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New brain atlases will unlock mysteries of the human mind
A suite of new studies unveils a detailed look of the brain and what it's made of — a leap towards understanding brain diseases.
In a massive effort to understand the human brain, scientists have revealed hightly detailed atlases of the brain — published through a suite of 21 papers on Thursday.
Ever wondered if your brain is just wired differently from others? You might be right. The new studies tackle how our brains operate at the cellular level.
Experts say the studies will help further our understanding of the brain and mind, and solve mysteries around diseases like Alzheimer's disease, schizophrenia, and depression.
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"This collection of studies is an attempt to understand the human brain, and its development, on a much more detailed level. It focuses on the building blocks of the brain, starting with cells," said Joseph Ecker, a biologist at the Salk Institute, La Jolla, US, who led one of the 21 studies.
The studies are part of the US-led BRAIN Initiative, which aims to uncover the mysteries of the brain. It's one of several multi-billion-dollar projects around the world aimed at creating comprehensive brain atlases. These brain projects are neuroscience's version of the human genome project, which successfully mapped the first complete human genome in 2003, or NASA's James Webb Space Telescope, which is changing our understanding of the universe.
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Don't we already have a map of the brain?
Anatomists have spent centuries creating atlases of the brain — mapping its subdivisions, folds (gyri) and grooves (sulci) for centuries.
Newer techniques have shown us beautiful images of the cellular structures of the brain's inner regions.
But our understanding of the brain was fragmented. The anatomical maps lacked information about how the cells functioned. And this functional information lacked precise spatial details.
More recently, neuroscientists turned their efforts to understanding how these brain cells, and the regions they are in, function — how they contribute to emotions, vision, or pain, or to disease states like schizophrenia or dementia.
"We didn't have a comprehensive view of a normal brain with enough detail to help us understand brain diseases. We're now getting closer to this," said Patrick Hof, a neuroscientist at Icahn School of Medicine at Mount Sinai, New York, US, who led one of the BRAIN Initiative studies.
Brain cell atlas with unprecedented details
What's new about this initiative is that it connects the brain anatomy with the function of its cells.
"It's a first dive into deeply understanding the human brain at the cellular level," Ecker told DW.
Each study helps to create different cartographies of the brain, with each map providing complementary information about the brain. The maps tackle the brain at different scales — from genes, to cells, to cellular structures, to larger brain regions, and finally the brain as a whole.
These maps integrate our varied knowledge about the brain and will be critical for unraveling its complexity.
Ecker's study, for example, created a highly detailed map of gene expression in different cells types in the brain, creating "bar codes." He also tracked how they change during development. It highlighted tremendous diversity in cells of the brain.
Hof's study, meanwhile, created a Google maps-like tool of Broca's area; a region of the motor cortex that controls speech and language.
Treating brain diseases is the ultimate goal
While the BRAIN initiative is "blue sky science" aimed at open discovery, scientists hope the research will eventually help to understand and treat brain diseases.
"Treating diseases is absolutely our end goal. But to understand brain diseases, we first need to know what's happening in a normal brain. That's our aim here,” Hof told DW.
What's important here, Hof said, is that we create atlases of the brain through its development — from fetal stages to old age. Only then can we fully understand what went wrong in the brain.
"It means we can understand what happens in developmental disorders like autism spectrum disorders, psychiatric diseases like depression and schizophrenia, and neurodegenerative diseases like Alzheimer's disease and Parkinson's disease," he told DW.
Ecker is also hopeful the studies will help create new applications to treat these diseases.
"It means we can create new tools to target the cell types that are affected in a certain disease. For example, it can help us to create better gene therapies that treat Alzheimer's disease. The treatments would be very specific," said Ecker.
Scientists working together
While the studies are helping to integrate our fragmented knowledge of the brain, the BRAIN initiative itself has helped to integrate the fragmented neuroscientists community.
"It was both a scientific and cultural shift for so many neuroscientists to work together on a project the same scale as the human genome project. It's working pretty well and there really aren't any arguments. That's a story in itself," Ecker said.
Collaboration between the other brain projects in the EU and Japan has also been successful, where open-access data and tools are helping scientists move towards the common goal of treating brain diseases.
"We are taking away boundaries between different disciplines in neuroscience. It's a tremendously important aspect that's opening doors to new discoveries," said Jan Bjaalie, a neuroscientist at the University of Oslo, Norway. He is the neuroinformatics leader of the EU-funded Human Brain Project, the European counterpart to the BRAIN initiative.
Bjaalie, who was not part of the 21 studies from the BRAIN Iniative, said they were an "outstanding contribution" to brain mapping efforts.
The new studies are currently a first draft of the human brain. The BRAIN Initiative aims to present its first complete atlas of the mouse brain in early 2024, with the human brain to follow in later years.
"The reason for these brain projects is the same reason for our interest in the universe: it is curiosity driven, but also driven by the need to understand brain diseases," said Bjaalie.
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Most Detailed Map Of Human Brain Created By Harvard, Google Scientists
Ten years ago, Dr. Jeff Lichtman, a molecular and cellular biology professor at Harvard University, received a little brain sample in his laboratory. Despite its small size, one cubic millimetre of tissue might hold 57,000 cells, 230 millimetres of blood arteries, and 150 million synapses. Lichtman and his team eventually obtained 1,400 terabytes of data from the sample, which is roughly equivalent to the content of more than 1 billion books.
Following a decade of close work with Google scientists, the lab team's data has resulted in the most precise map of a human brain sample ever made.
Where did the brain sample come from?
The brain sample was obtained from a patient with severe epilepsy. Lichtman explained that it is the usual procedure to remove a little bit of the brain to halt the seizures and then examine the tissue to ensure it is okay.
"But it was anonymized, so I knew next to nothing about the patient, other than their age and gender," he stated.
What did the scientists do to the brain sample?
To analyze the sample, Lichtman and his team first sliced it into thin slices with a diamond-bladed knife. The parts were then implanted in a hard resin and chopped very thinly.
"About 30 nanometers, or nearly one thousandth the thickness of a human hair. They were almost invisible if we hadn't dyed them with heavy metals, which made them visible when undertaking electron imaging," he explained.
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The crew ended up with several thousand slices, which were picked up with custom-made tape to create a type of film strip: “If you take a picture of each of those sections and align those pictures, you get a three-dimensional piece of the brain at the microscopic level.”
How did scientists at Google help analyze the data?
To make sense of the photos, Google scientists utilized AI-based processing and analysis to determine what kind of cells were present in each image and how they were connected.
The end result is an interactive 3D model of brain tissue, as well as the largest dataset of human brain structure ever created at this resolution.
Google made it available online under the name "Neuroglancer," and research was published in the journal Science at the same time, with Lichtman and Jain as co-authors.
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