Exploring how this huge long-term investment, one of the most ambitious digital neuroscience projects in history, is starting to pay dividends by inspiring innovation
Back in 2021, a paper recently published in The Lancet [1] defined the impact on human life of disorders affecting the nervous system. Neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment, were among 37 conditions reviewed. The results were chilling.
In 2021, an estimated 3.4 billion people—43% of the global population—had a condition affecting the nervous system. These conditions contributed to more than 11 million deaths and 168 million years lived with disability, as well as 275 million years of life lost between 1990 and 2021. In short, more than 443 million disability-adjusted life-years are the result of neurological conditions.
This problem will only get worse as life expectancy around the world increases and population rises. To live is one thing, but to live well is another. Mental disorders and brain diseases are on the rise, so brain health is rapidly climbing the agenda as the emphasis falls on quality of life for aging populations.
“Extrapolation from current statistics suggests that by 2030 mental disorders will become a huge cost factor, larger than all other cost factors combined,” says Dr. Viktor Jirsa, director of the Institut de Neurosciences des Systèmes (INS) at Aix Marseille University in France. “I compare mental disorders and brain disease to climate change—a situation we can predict will occur and which will be catastrophic unless we take action now.”
The Human Brain Project (HBP), started back in 2013 and completed in September 2023, is a key pillar of Europe’s efforts to tackle this problem head on. Its aim was to pioneer a new paradigm in brain research by laying down the technical foundation for a new model of information and communication technology (ICT)-based brain research. This model would drive the integration of data and knowledge from different disciplines, and catalyze a community effort to achieve an unprecedented understanding of the brain and generate new therapies.
This was no small undertaking, but its backers knew that aiming high was the only option.
“The human brain is one of the most complex systems that can be researched,” says Prof. Katrin Amunts, director general of HBP (Figure 1). “It is comparable to researching the development of the universe. The high complexity of brain organization is reflected in large data sets that must be integrated to obtain a coherent picture. This was the motivation to develop EBRAINS—a digital platform to handle and analyze large and complex data.”
Figure 1. Katrin Amunts, director general of the HBP. (Photo courtesey of Human Brain Project.)
“You can only think about developing therapies in a targeted way when you understand the system,” she adds. “Personalized therapies are necessary, but are also challenging, since brains differ in structure and function just like people differ in their appearance. Modeling and simulation can help to develop personalized therapies, for instance by simulating a certain condition before a drug is administered or surgery starts. Novel digital tools are, therefore, the basis.”
The unprecedented power of EBRAINS
Once the right software and hardware had evolved to handle such an ambitious project, the next step was to integrate that technological infrastructure with the existing knowledge of the human brain. This meant combining many areas of research that had previously been disconnected.
Neuroscience falls into many silos—cellular, functional, behavioral, evolutionary, computational, molecular, cellular, and medical—and there are many other approaches to understanding the brain. Neuropsychology, for example, studies the physiological processes of the nervous system and relates them to behavior and cognition.
“We wanted to bring all of the different branches together, which meant creating the right culture and the right processes for collaboration, as well as the right technical tools to enable a better understanding of how the brain works,” Amunts continues.
The key output from HBP is EBRAINS, a digital platform for collaboration where researchers can access and use atlases of the brain, medical analytics, modeling and simulation capability, and vast amounts of data. Using a distributed computing infrastructure including supercomputer and neuromorphic computer resources, researchers can share knowledge to build revolutionary simulations of the brain’s response to new therapies.
EBRAINS, which already has around 10,000 subscribers, relies heavily upon atlases of the brain. Alongside her role as Director General of HBP, Amunts is also head of the Julich Brain Atlas.
“It is like Google Maps for the brain,” she explains. “It provides a 3D view of structures across different brains, from the organ level down to the level of single cells, enabling it to reflect brain complexity on many different levels. Ten years ago, we had maps of 40 or 50 different areas, and it took one year for a person to map a single area. Now we have mapped more than 200 areas of the brain” (Figure 2).
Figure 2. Brain atlases combined with advance simulation and modeling yield high-resolution models at organ or cellular level for use in evaluating therapeutic impact. (Image courtesy of Human Brain Project.)
“It is the most comprehensive microstructural map in existence,” she adds. “It is like using Google to not only see where you are, but also what the weather conditions are, and being able to book a table in a restaurant. It is the basis of a framework for surgeons to understand the territory of the brain—and not an average brain, but a personalized brain, when the atlas is linked with patient brain modeling technologies on EBRAINS.”
EBRAINS and the atlas speak volumes about the success of the HBP and its promise for future innovation.
“We now have a much clearer view of the human brain than when the project started,” believes Jirsa. “It began as a technology-driven ICT project that was supposed to find applications to improve our understanding of fundamental neurosciences, but looking back, the value of HBP is that it took a pioneering and forward-looking approach in pursuing a computational understanding of the brain.”
“It goes beyond what it promised in the early days,” he adds.
Inspiring innovation
With a host of collaborative tools seamlessly linked under one umbrella, EBRAINS is enabling researchers to tackle the sheer complexity of the human brain, leading to some impressive outcomes.
A prime example is the work of Jirsa’s team on epilepsy. Currently, around 1% of the human population has epilepsy, of whom 40% cannot be treated chemically, leaving surgical intervention as the alternative. The procedure requires the precise identification of tissue blocks that must be removed to make a patient seizure-free, but must remove as little as possible to limit collateral damage.
Jirsa and his group at INS co-created the virtual epileptic patient (VEP), a virtual brain neuronal model that uses a simulation engine on EBRAINS, along with brain atlas data informed by neuroimaging data for an individual patient, to identify where in the brain that individual’s seizures are likely to be generated. That information is used to create a model for the surgeon.
The VEP, which is undergoing clinical trials, is just one example of how the multi-scale and multi-modal atlas generated from the HBP is able to conceptually connect the molecular or microscopic and macroscopic views of the network that carries brain function. The model can also be used to predict the effects of drug therapies, brain stimulation or surgery because a virtual brain for a specific human subject—a digital twin—can now be constructed using brain imaging data.
During the clinical trial, VEP has been used for around 400 patients, all of whom were visualized through neuroimaging data to create digital brain twins that surgeons could use in their decision-making process.
“Epilepsy is a good entry point and has helped us to drive the science further, but other applications are now emerging,” Jirsa explains. “The low-hanging fruit are applications to do with brain stimulation, which is often a matter of trial and error, so a brain model could help optimize it for the patient and the disease.”
“Parkinson’s disease is one of the candidates but so are obsessive compulsive disorder (OCD), pharma-resistant depression and other conditions that sometimes require stimulation,” he adds. “We have just received funding for a virtual brain project for schizophrenia patients.”
Researchers are already investigating deep brain stimulation for Parkinson’s patients who are not responding to drugs and need electrodes implanted in the brain. Once again, a digital brain twin could help surgeons understand cell distributions and networks to locate implants and stimulate the right areas to limit tremors.
Elsewhere, Prof. Dr. Giulia Rossetti, group leader of the Drug Design Hub for Digital Neuropharmacology, Forschungszentrum Jülich, und RWTH Aachen, is using EBRAINS and the Fenix infrastructure—a collaboration between six major European supercomputing centers—to investigate the efficacy of drug candidates to bind to their targets and treat neurodegenerative diseases.
“What came out of HBP is a vision for a future roadmap of where neuroscience should go,” says Jirsa. “In 2010, people were not talking about digital twins, but now it is a buzzword everywhere. HBP has advanced the concept of fusing empirical data with digital models and simulations.”
“With more therapies relying on data and models, we expect the advantages to come in the form of better outcomes,” adds Amunts. “You can test treatments before you go into surgery, and surgeons can play around with different scenarios before they open the skull. Surgeons are better prepared, and the treatments are more cost-efficient.”
EBRAINS is not a closed or completed system. It is a living and evolving infrastructure that will continue to grow through future iterations. It is the fruit of an ongoing dialog between science and digital technology, neither of which ever stand still.
The technological infrastructure will improve, the use of digital twins will become more sophisticated, more projects will come online, and digital neuroscience will steadily become the norm. Whatever emerges next from the HBP, the project has already had a profound impact.
“EBRAINS needs to be carried forward by the world’s scientific community,” says Jirsa. “I hope it will be a turning point, and I am happy to dedicate the rest of my scientific life to this. Its success will be a witness to the legacy of the HBP.”
Jirsa is far from alone in his passion for EBRAINS. The European neuroscience community is embracing this revolutionary tool, the impact of which will no doubt reverberate around the world.
Reference
- “Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: A systematic analysis for the Global Burden of Disease Study 2021,” Lancet, vol. 23, no. 4, pp. 344–381, Apr. 2024. [Online]. Available: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext