Researchers have been studying the brain for ten years, so what are the results?
The world’s largest brain research project has made some progress, but schizophrenia and Alzheimer’s have not yet been defeated. Actual progress is different.
Essential though supercomputers: A special microscope helps analyze a section of the brain in the laboratory.
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To approach this problem, one can imagine brain researchers as advanced aliens who have just discovered Earth. What a beautiful blue planet! Dear researchers, you will now get a lot of coal, then – please – explain to us about the earth and what you can do with it. You have ten years.
Soon he will fight the aliens. Some might call for landing on Earth as quickly as possible and collecting data, for example on the very interesting social life of ants, which are clearly the most successful life form on the planet. Other space researchers may first want to look at the big picture: climate, tides, continental drift, geo-environmental cycles, and waves of migration. Shouldn’t we let the satellites do the remote sensing first?
One hundred billion neurons
Brain research faces similar questions. Without straining the image: they present typical problems when dealing with very complex systems – the human brain is perhaps the most complex system of all. Eight billion people live on Earth, and each brain contains approximately one hundred billion neurons, all of which are interconnected. It’s not easy to come up with a theory for everything.
Bottom-up and top-down approaches have also competed for a long time in neuroscience. Bottom up means first examining the smallest units, neurons and their connections. On the other hand, top-down means starting with cognitive functions. It is not easy to combine the two. Most of his colleagues therefore found it reckless to do so Brain researcher Henry Markramthen at the École Polytechnique Fédérale de Lausanne, proposed a revolution around 2010: scientists like him wanted to emulate the entire human brain, with its billions of neurons and trillions of synapses, from bottom to top, one-by-one in a computer model and, at the same time, develop therapeutics. For Alzheimer’s disease and schizophrenia.
“With the Human Brain Project, a supertanker was set in motion, but when it set off you didn’t know where it was supposed to go.”
In fact, the charismatic Markram has managed to secure one of the few so-called flagship projects in the EU: as of the fall of 2013, the European Commission has made available a total of €600 million for the Human Brain Project (HBP) for ten years. It was clear from the beginning what will be clear in the fall of 2023: Markram had failed to see it. “This was just a hope for the holy grail of brain science: a science fiction of omnipotence,” says Andreas Dragun, a neurophysiologist at Heidelberg University School of Medicine.
Henry John Markram is the director of the Blue Brain Project and founder of the Human Brain Project.
Photo: Laurent Giraud
As early as July 2014, 800 scientists criticized the management of the HBP project and the opaque allocation of research funds. Particularly disturbing was that the initial funding cuts were primarily at the expense of a top-down perspective. Researchers should focus primarily on neurons, synapses, and their digital simulations. The view from above on thinking, perception, and all of cognition has to take a back seat. In addition, researchers excluded from the HBP project feared that financial support in Europe would focus on this large-scale project, at the expense of smaller-scale research projects. “The HBP was used to move a supertanker, but when it set off it didn’t know where it was supposed to go,” Dragon complains. “It was important to think about this while at the same time supporting smaller, creative research projects.”
“We are still walking in the dark with flashlights, exploring individual questions.”
Andreas Herz, professor of computational neuroscience at Ludwig Maximilians University in Munich, sees the same thing. At the time, people were drawing inspiration from other giant projects, such as the Large Hadron Collider (LHC), the particle accelerator at CERN’s Physics Research Center in Geneva, or the Human Genome Project in biology. “However, compared to physics, neuroscience is still far ahead of what it was in 1920,” concludes Herz.
This can already be seen by the type of posts. “Neuroscientists usually report new and unexpected phenomena they have discovered,” says the Munich researcher. “We are still walking in the dark with flashlights, exploring individual questions.” On the other hand, physicists were able to bask in the bright light of a universal unified theory when the LHC was built. “They are delighted with every little discrepancy between theory and experiment that can still be found, because it pushes them forward step by step.”
A comprehensive theory is missing
Neuroscience has lacked a comprehensive theory that can, like the theory of fundamental interactions in physics, explain large parts of the observations. “The theoretical deficit is very severe,” Dragon says. “There is not even agreement about what we mean by central concepts, by memory, by perception, and certainly not by consciousness.” Instead, there are “a lot of unclear computer metaphors.” “In this respect, the Human Brain Project certainly came too early,” says Andreas Herz.
However, the massive research project has made significant progress – perhaps due to the rapid response to early criticism. At the beginning of 2016, Katrin Amunts, professor at the University of Düsseldorf and Research Center Jülich, became Scientific Director of the HBP. She first put the tanker at anchor and dealt with the basics of navigation. Among other things, the participating working groups have built the largest brain atlas to date, which can be accessed by all interested researchers via the so-called Ebrains platform. “This now makes it possible to integrate digital tools into complex, reproducible research work,” says Amunts. “This facilitates collaboration between different neuroscience disciplines.”
“This is a win-win and has great potential,” emphasizes Andreas Dragon from Heidelberg. So there is no longer just a large tanker, there is increasingly large-scale data material that the armada of all brain researchers can use. This is more than justifiable in hindsight, as Amuntz asserts: “Developing this collaborative research infrastructure would have required technical effort and substance, and it took the shape and duration of the flagship to seriously implement this goal.”
Catherine Amunts took over the Human Brain Project as Scientific Director in 2016.
Photography: Maren Fischinger (Jülich Research Center)
It is now finally possible to aggregate complex and rapidly growing amounts of data, analyze it together and make it available to others. “Just as in astrophysics, where not only the operator of the most powerful telescope analyzes complex data, but many research groups have access to it,” says Amunts. This is the real progress made by the HBP: “to better understand the multi-scale and multi-modal nature of the brain using new digital methods.” It sounds technical and flimsy, but it’s important. The original bottom-up accusation against the HBP is no longer appropriate. Rather, it is about relating properties of brain organization across many scales of size.
So what remains after ten years of HBP? No one has even come close to mimicking the human brain. Neither schizophrenia nor Alzheimer’s disease has been overcome. But the project should not be measured solely by the overly ambitious promises made at the beginning. New data infrastructure is key, and exciting medical projects have emerged. It is now easier to assess the state of consciousness of people with brain injuries. Progress has been made in digital implants for paralyzed and blind people. New brain models improve precision in epilepsy surgeries
“Many people have found funding for good, meaningful projects under the large umbrella of HBP.”
The fear that smaller research projects will be neglected may not have been confirmed. At least no participant could mention a hot little project whose funding failed due to the €600 million provided to HBP. “You have to be honest, many people have found funding for good and meaningful projects under the big umbrella of HBP,” says Andreas Dragun.
The future roadmap for neuroscience must now be discussed. The vision that minds on Earth could one day understand themselves remains fascinating. “You can also call it a model if you’re bothered by the term vision,” Amuntz says. But it’s important to “discuss ambitious goals in research as well, otherwise you’ll be left standing.”
Hardly anyone thinks of a complete replica anymore
But hardly anyone thinks about fully replicating the brain anymore. “Even if we could create a kind of digital copy of the entire brain,” asks neuroscientist Herz, “what would that do to us?” “We won’t understand them.” It’s the same as with paper maps: they are unwieldy on a one-to-one scale. “Models have to be intelligently simplified to be usable,” says Herz, who doubts that we will ever be able to fully understand the brain. The dynamic processes conducted by more than one hundred billion neurons and glia, which often communicate with each other through shorter and very long processes, are extremely complex. “How can an event that lasts a few seconds sometimes stay with us for the rest of our lives?” Herz asks.
Theories and experiments will continue to shed light on feeling and thinking in the future. They are unlikely to form a large, coherent theory of the brain. “I think the best we can achieve is a mixture of models at many spatial and temporal scales, a colored glass mosaic through which the neurobiological reality shines,” says Andreas Herz. “It doesn’t bother me. This is the truth of nature. This is life.”
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