Year 1 Achievements

HBP ACHIEVEMENTS YEAR ONE

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As the first year of its Ramp-Up Phase draws to a close, the HBP is well-placed to expand the frontiers of neuroscience, medicine, and computing. With hiring of staff complete, the coordination of the Project is shifting into high gear. Reporting of Milestones and Deliverables to the European Commission has been complete and timely. Competitive calls have brought in new Partner institutions to many of the Subprojects (SP), bringing new knowledge and exciting contributions. Here are some of the scientific and organisational highlights from Year 1 of the HBP Flagship.

HBP ACHIEVEMENTS – YEAR ONE

Using a combination of molecular and cellular approaches, SP1 researchers are systematically generating data to fill key gaps in our knowledge on the structural organisation of the mouse brain.

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STRATEGIC MOUSE BRAIN DATA

• Single-cell transcriptomics: Methods for identifying all the genes expressed in single neurons have been developed and tested, making large-scale screening of the genetic types of cells in the mouse brain technically feasible. Initial single-cell transcriptomes suggest that each neuron expresses 3-4,000 of roughly 20,000 total genes.

• Proteomics and genetic databases: Existing neuronal, glial and synaptic proteomics and gene expression databases have been identified and prepared for integration with the HBP Platforms.

• Electron microscopy mapping: The first electron microscopy scans of tissue from cortex and hippocampus have yielded quantitative data on synapse densities, of vital importance for brain modelling.

SP1

• Automated cell and labelled puncta counting: The Project has established a prototype method for automated counting of fluorescently stained neurons and puncta in the whole brain.

• 3D reconstruction methods of neurons, axonal projections and blood vessels: Methods of 3D reconstructions have been set up and refined to yield strategic anatomical data for brain modelling.


SP2 researchers generate data on the structure and function of the human brain.

• New brain imaging methods: Connectivity Analysis is a new MRI-based technology that uses the different diffusion times of water molecules to assess axon diameters. Polarized Light Imaging has yielded the first 3D microscopic reconstructions of axon orientation in the human temporal lobe.

• BigBrain reconstruction: A human post mortem brain has been processed, 3D reconstructed, and published as the BigBrain data set (Amunts et al., Science, 2013). The challenges of unifying different scales and data types into a common reference system for human brain modelling are outlined by Amunts et al. in Neuroimage (2014).

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STRATEGIC HUMAN BRAIN DATA

• Brain mapping named one of the Top 10 Breakthrough Technologies of 2014: BigBrain was recognised by MIT Technology Review (http://www.technologyreview.com/featuredstory/526501/brain-mapping)

• Neuron morphologies differ between human, mouse and monkey: Histology of human pyramidal neurons shows that they are very different from equivalent cells in mouse and monkey brains. Human temporal cortex neurons have more dendrites and show high-frequency spike timing, and human action potentials remain faster during repeated firing (Eyal et al., Journal of Neuroscience, in press).

• Neurotransmitter receptor expression levels differ in language and non-language regions: Multi-receptor fingerprints were extended to human primary sensory and motor regions. The density

SP2

of cholinergic muscarinic M2 receptors was tracked in more than 50 brain regions, demonstrating the feasibility of the mapping approach.

• Maturation of white matter bundles in infancy: To improve developmental models of brain connectivity, an infant reference template covering 94 regions and external anatomical landmarks has been published (Kabdebon et al., Neuroimage, 2014).

• Eight functional localisers defined: The first 8 fMRI protocols collected from the international community to map a large number of cognitive systems have been tuned.

• Maximum probability map for data deposition: A new update of cytoarchitectonic probabilistic maps, developed in JUELICH and UDUS, has been created and used to generate a maximum probability map.


SP3 researchers study the brain regions, structures and circuits involved in cognitive tasks, and the underlying principles of information processing.

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COGNITIVE ARCHITECTURES

SP3

• Circuits linking perception to action, body perception and sense of self: Electrocorticography (ECoG) signals from perceptual and visuo-motor tasks have yielded important insights into the use of specific frequency bands for carrying forward and backward visual signals. A new neurodynamic model for multi-stability of action perceptions has been compared to experimental data. Advances have been made in the anatomical dissection of the parietal operculum, the inferior parietal cortex and adjacent parts of the superior temporal gyrus based on existing brain imaging data on bodily self-consciousness.

• Architectures for Decision and Confidence: A new task has revealed behavioral evidence that human subjects can based both primary decisions and confidence judgments on close-to-optimal computations with statistical distributions.

• Architectures for learning and memory: An understanding of how working memory and real-life episodic consolidation starts in the human hippocampus has been established. The first model of the generation of “spindle-ripple events”, which mediate the transfer of reactivated memory information from hippocampus to extrahippocampal circuitry during sleep, has been developed.

• Architectures for spatial navigation and decision-making: Architectures have been developed and validated with experiments on rodent and human navigation and spatial memory tests. Neuroimaging methods for locating components of spatial memory have been developed (Kaplan et al., Hippocampus, 2014).

• Architectures for language, syntax, and social brain: New fMRI experiments have been designed, and subjects have been scanned, to isolate the neural correlates of language and mathematical syntax, and interpersonnal representations.

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SP4 applies mathematical techniques to produce top-down models of the brain across different scales and to understand the basic principles. underlying cognitive functions.

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THEORETICAL NEUROSCIENCE

SP4

• The European Institute for Theoretical Neuroscience: EITN (www.eitn.org) is hosted by the Institut de la Vision in Paris and has been in operation since March 2014. The Institute has organised numerous workshops with HBP and non-HBP partners. The institutional inauguration on 18 September 2014 was attended by, among others, Thomas Skordas, head of the European Commission’s Flagship unit.

• Initial simplified models: Simplified neuron models that account for dendritic input processing have been completed.


The Neuroinformatics Platform gathers and organises the massive volumes of heterogeneous data, knowledge and tools produced by the international neuroscience community.

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NEUROINFORMATICS PLATFORM

SP5

• The Neuroinformatics Platform: The architecture and user specifications of the Platform have been developed and published as a Deliverable. Development has started and an internal draft is on schedule for release to the HBP Consortium in mid-2015.

• ESPINA software: A new version of the ESPINA software was released. This software is used for automated segmentation of data in electron microscopy image stacks.

• Data sets assembled: Data on neuronal, glial and synaptic proteomics, neocortical microcircuitry, whole mouse brain, and whole brain tracts have been identified and are being integrated into the first draft of the Neuroinformatics Platform.

• Data collaborations: Collaboration with the Allen Institute for Brain Science is underway in the areas of standard protocols, quality control and metadata standards and modelling. A memorandum of understanding was signed with the Visible Brainwide Networks Project from the Britton Chance Center for Biomedical Photonics in Wuhan, China for collaboration on whole brain rodent data and feature extraction. In addition, a collaboration has been initiated with the newly funded Australian Research Council Centre of Excellence for Integrative Brain Function based in Melbourne, Australia.


The Brain Simulation Platform allows researchers to reconstruct biologically detailed models of the brain, and to simulate the behaviour of the models on supercomputers.

• HBP Unified Portal: A first working prototype of the Unified Portal is ready for internal testing by the Consortium. The Unified Portal is a single point of access to all six HBP Platforms.

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BRAIN SIMULATION PLATFORM

SP6

• The Brain Simulation Platform: The architecture and user specifications of the Platform have been developed and published as a Deliverable. Development has started and an internal draft is on schedule for release to the HBP Consortium in mid-2015.

• Brain simulation software: HBP efforts have been aligned with community-driven roadmaps for the NEST, NEURON, and STEPS simulators, ensuring long-term viability and global community participation. In its first year, the HBP has achieved substantial scale-up of NEST on massively parallel computers (Kunkel et al., Frontiers in Neuroinformatics, 2014), a reduction of the memory footprint by a factor of six in NEURON, and advances in the parallelisation of STEPS.

• Molecular models: Prototype software and workflows have been developed for automated loading, distribution and

specification of reactions between molecules in neurons.

• Cellular models: The automated modelling of neuronal firing behaviour developed on neocortical neurons has been tested on the most complex neuron — the cerebellar Purkinje neuron — and also on human pyramidal neurons.

• Microcircuits: A first draft cellular and synaptic reconstruction and simulation of the rodent somatosensory microcircuit with 207 different cell-types and 40 million synapses has been completed and released through an online portal.

• Mesocircuits (brain regions): Simulation of a part of the rodent neocortex with 3 million morphological detailed neurons and 400 million dynamic synapses has been achieved. A first draft reconstruction of the cerebellar network of neurons has also been made.


The High Performance Computing Platform provides the supercomputing capabilities for multi-scale brain modelling, simulation and data analysis.

• The High Performance Computing Platform: The use cases, requirements and architecture of the Platform have been specified and published as a Deliverable. Development has started and an internal prototype is on schedule for release to the HBP Consortium in mid-2015.

• Operational supercomputers: Four HBP supercomputers are ready for use by the HBP (the HBP Supercomputer for Brain Modelling and Simulation

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HIGH PERFORMANCE COMPUTING PLATFORM

SP7

at JUELICH in Germany, the HBP Massive Data Analytics Supercomputer at CINECA in Italy, the HBP Molecular Dynamics Supercomputer at BSC in Spain, the HBP Development Supercomputer at CSCS in Switzerland).

• Cloud storage: An S3 storage service has been set up for testing purposes at KIT (Germany) and will be made available to users by the end of September 2014.

• Large-scale simulation: Models with 3 million morphologically detailed or 1 billion point neurons can now run routinely on the supercomputers at CSCS and JUELICH, respectively.

• Interactive supercomputing technologies: Real-time streaming between CSCS and EPFL (Lugano and Lausanne in Switzerland) for the NEURON simulator has been established.

• Pre-Commercial Procurement of specific HPC solutions for the HBP to support interactive supercomputing underway: The call for tender was published in April 2014 and closed after seven weeks. Successful bids have been selected and the tenderers were notified in August 2014.

• Software development: A prototype tool for indexing exascale spatial data sets is ready to be deployed on the Platform. Libraries for streaming simulation data to visualisation and for streaming remotely generated imagery content to high-resolution display walls have been developed. A first version of the coarse-grained programming model PyCOMPSs has been developed and is already in use.


The Medical Informatics Platform provides researchers nside and outside the HBP with access to anonymised patient data.

• The Medical Informatics Platform: The architecture and user specifications of the Platform have been developed and published as a Deliverable. Development has started and an internal draft is on schedule for release to the HBP Consortium in mid-2015.

• Web portal and MIP services: The services (epidemiological exploration, interactive analyses, biological signatures of diseases) allow researchers to form queries or launch complex analyses on the anonymised data in the local data nodes, via the federation layer.

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MEDICAL INFORMATICS PLATFORM

SP8

• Federated querying/processing: Detailed evaluations (demo, proof of concept) have been started with eight major international companies for the federation sub-contract. A complex dataflow-process-ing engine for distributed computation has been designed and developed.

• Local data store: Specification of the tools for data extraction and integration of patient data have been established and implemented in one hospital (CHUV). The requirements analysis for the anonymisation of patient data and the pre-selection of candidate solutions has been completed. Architecture of HBP-MIP local nodes, including databases and a query engine, has been defined and a prototype created.

• Data acquisition: MRI and genetic data on 6,000 patients have been gathered from large-scale research studies,

clinical cohort studies and pharmaceutical trials. The MIP database includes data of 8,305 patients from CHUV (Switzerland).

• Data mining: Preliminary data mining experiments have been performed on the research data sets. A data mining strategy has been developed with expert medical input. Various algorithms have been combined in an iterative fashion to generate a disease-ome defined by clinical and biological data and to promote precision medicine.

• Hospital recruitment: 18 hospitals have expressed interest in using the Platform.


SP9 is designing a new category of computing hardware inspired by the circuitry of the brain.

• The Neuromorphic Computing Platform: The architecture and user specifications of the Platform have been developed and published as a Deliverable. Development has started and an internal draft is on schedule for release to the HBP Consortium in mid-2015.

• Two complementary neuromorphic systems: Construction in Manchester and Heidelberg has progressed on schedule. During the first year 100,000 ARM processors of the Many Core System and a complete wafer module of the Physical Model System have

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NEUROMORPHIC COMPUTING PLATFORM

SP9

been manufactured. The rack systems, power and cooling infrastructures of the systems are ready for installation of the compute units.

• Demo of HBP custom neuromorphic hardware: A first public live demonstration of the unified HBP neuromorphic user workflow will be shown at the HBP Summit in October 2014. Both neuromorphic hardware systems (NM-MC-1 in Manchester, NM-PM-1 in Heidelberg) have been integrated into a common software workflow for unified user access as part of the HBP Platform concept.

• Portable neuromorphic systems: For both hardware systems, small-scale portable neuromorphic computing devices have been produced. These devices are USB add-ons for conventional laptops and are now in use by outside groups and students to explore the potential of neuromorphic computing.

• Next-generation chips: New prototype chips of the neuromorphic systems have been developed for both hardware systems. The prototypes represent key ingredients for the realisation of the detailed Neuromorphic Platform roadmap that defines the technical specifications of the Platform until 2023.

• Neuromorphic chips named one of the Top 10 Breakthrough Technologies of 2014: Brain-inspire computing recognized by MIT Technology Review as one of the major breakthroughs in 2014 (www.technologyreview.com/featuredstory/526506/neuromorphic-chips/)


The Neurorobotics Platform is a high-fidelity simulation system for virtual robotics that allows neu-roscientists and other non-robotics researchers to perform in silico cognitive and behavioural neuroscience experiments. The Neurorobotics Platform connects HBP brain models to simulated robot bodies for testing, training, and experimentation.

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NEUROROBOTICS PLATFORM

SP10

• The Neurorobotics Platform: The architecture and user specifications of the Platform have been developed and published as a Deliverable. Development of the Platform has started and the first version will be ready for internal release to the HBP Consortium in in mid-2015.

• Platform software foundations: The Neurorobotics Platform builds on well-established open source projects with large developer and user communities. Suitable open source projects have been found for all parts of the Platform and have been successfully integrated into the development system.

• Robot and body models: Several mobile robot models have been integrated and tested in our development system. In addition, a first prototype of a virtual mouse body model has been developed.

• Environment models: A complete virtual room, including furniture and computer screens, was created and added to the development system.

• Closed loop simulation: The first closed-loop simulations have been run on our development system. The simulations include a robot that moves inside the virtual room and is controlled by a simple point neuron network.


SP11 is performing small-scale pilot projects to test and refine the HBP’s ICT Platforms.

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APPLICATIONSSP11

• Future Medicine: Study of cognition, brain anatomy, and genetics in 500 elderly patients with and without dementia.

• Future Computing: Implementing data mining algorithms in neuromorphic hardware, starting with algorithms for temporal sequence learning.

• Pilot Projects in progress: These pilot projects encompass the three HBP research arms (neuroscience, medicine and computing).

• Future Neuroscience: Closed loop experiments using retinal models as input to models of cortex.


SP12 is exploring the social, ethical and philosophical implications of HBP research, promoting engagement with decision-makers and the general public.

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ETHICS AND SOCIETYSP12

• Committees: The Research Ethics (REC) and Ethics, Legal and Social Aspects (ELSA) Committees are in operation. The ELSA and REC committees held inaugural meetings in March 2014 in Paris.

• Conferences on consciousness and epistemology and simulation: The first in an ongoing cycle of public meetings brought together HBP scientists and researchers in the social sciences, philosophy and ethics. The first conference, held in February 2014 at the Institut Pasteur in Paris, asked the question: “How can neurotech-nology - notably brain simulation as developed in the HBP - help assess, understand and access consciousness?” The second conference in June 2014 was on “The Epistemology of Simulation: How can in silico simulation help understand and reproduce complex processes such as higher brain functions?”

• First stakeholder forum: Topics included Multi-level data federation and data protection, and Disease signatures and personalised medicine. This event in May 2014 explored the concepts of privacy, informed consent, and anonymisation, and initiated a constructive dialogue between SP8 researchers (Medical Informatics) and specialists in law, ethics, and the social sciences.

• Survey of ethical awareness in the leadership of HBP: Qualitative interviews with senior staff were conducted to determine the major ethical and social issues facing the Consortium. The findings will be presented in detail in the forthcoming report in November 2014.


SP13 supports decision-making, operates the management structure, ensures transparency and accountability, and maintains standards of quality and performance.

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MANAGEMENTSP13

• Governance: All HBP governing bodies are in operation.

• Management offices: The following core administrative functions are in operation: Relations and Innovation, Science and Technology Office, Communications Office, and Editorial Office. The HBP Competitive Call was successfully completed and 32 new partners were added to the Consortium through a contractual amendment.

• Annual Summits: Two HBP Summits have been organised (October 2013 and 2014).

• Proposals: The proposal for the Framework Partnership Agreement was submitted in June 2014. This document outlines the governance of the evolving Consortium beginning in 2016.

• Outreach: The HBP Museums Programme was launched.

• Education: The HBP Education Programme was launched. The first Workshop (Tel Aviv, June 2014) and the first Summer School (Innsbruck, September 2014) were held.

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Collaboration is at the heart of the Human Brain Project. Scientists and engineers working in individual Subprojects leverage each other’s strengths every day, and the Project’s success depends on collaboration among all Consortium Partners

SP11 SP12

SP10

SP1

SP2

SP3

SP4

SP5

SP6SP7

SP8

SP9

SP10

SP12

THE HBP’S EMPHASIS ON COLLABORATION IS EXEMPLIFIED

BY THE INTERDEPENDENCE OF ITS TWELVE RESEARCH SUBPROJECTS

Subproject 1 SP1 Strategic Mouse Brain Data – Subproject 2 SP2 Strategic Human Brain Data

Subproject 3 SP3 Cognitive Architectures – Subproject 4 SP4 Theoretical Neuroscience – Subproject 5 SP5

Neuroinformatics Platform – Subproject 6

SP6 Brain Simulation Platform – Subproject 7 SP7 High Performance

Computing Platform – Subproject 8

SP8 Medical Informatics Platform – Subproject 9 SP9 Neuromorphic

Computing Platform – Subproject 10 SP10 Neurorobotics Platform – Subproject 11 SP11 Applications

Subproject 12 SP12 Ethics and Society

/ HumanBrainProj

/ HumanBrainProj

www.humanbrainproject.eu

Documents

Year 1 Achievements