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Google helped make an exquisitely
detailed map of a tiny piece of the human brain
A small brain sample was sliced into 5,000 pieces, and
machine learning helped stitch it back together.
Researchers built a 3D image of nearly every neuron and its
connections within a small piece of human brain tissue. This version shows
excitatory neurons colored by their depth from the surface of the brain. Blue
neurons are those closest to the surface, and fuchsia marks the innermost
layer. The sample is approximately 3 mm wide. GOOGLE RESEARCH & LICHTMAN
LAB, HARVARD UNIVERSITY / D. BERGER (RENDERING)
A team led by scientists from Harvard and Google has created
a 3D, nanoscale-resolution map of a single cubic millimetre of the human brain.
Although the map covers just a fraction of the organ—a whole brain is a million
times larger—that piece contains roughly 57,000 cells, about 230 millimetres of
blood vessels, and nearly 150 million synapses. It is currently the
highest-resolution picture of the human brain ever created.
To make a map this finely detailed, the team had to cut the
tissue sample into 5,000 slices and scan them with a high-speed electron
microscope. Then they used a machine-learning model to help electronically
stitch the slices back together and label the features. The raw data set alone
took up 1.4 petabytes. “It’s probably the most computer-intensive work in all
of neuroscience,” says Michael Hawrylycz, a computational neuroscientist at the
Allen Institute for Brain Science, who was not involved in the research. “There
is a Herculean amount of work involved.”
Many other brain atlases exist, but most provide much
lower-resolution data. At the nanoscale, researchers can trace the brain’s
wiring one neuron at a time to the synapses, the places where they connect. “To
really understand how the human brain works, how it processes information, how
it stores memories, we will ultimately need a map that’s at that resolution,”
says Viren Jain, a senior research scientist at Google and coauthor on the
paper, published
in Science on May 9. The data set itself and a preprint
version of this paper were released
in 2021.
Brain atlases come in many forms. Some reveal how the cells
are organized. Others cover gene expression. This one focuses on connections
between cells, a field called “connectomics.” The outermost layer of the brain
contains roughly 16 billion neurons that link up with each other to form trillions
of connections. A single neuron might receive information from hundreds or even
thousands of other neurons and send information to a similar number. That makes
tracing these connections an exceedingly complex task, even in just a small
piece of the brain.
To create this map, the team faced a number of hurdles. The
first problem was finding a sample of brain tissue. The brain deteriorates
quickly after death, so cadaver tissue doesn’t work. Instead, the team used a
piece of tissue removed from a woman with epilepsy during brain surgery that
was meant to help control her seizures.
Once the researchers had the sample, they had to carefully
preserve it in resin so that it could be cut into slices, each about a
thousandth the thickness of a human hair. Then they imaged the sections using a
high-speed electron microscope designed specifically for this project.
Next came the computational challenge. “You have all of
these wires traversing everywhere in three dimensions, making all kinds of
different connections,” Jain says. The team at Google used a machine-learning
model to stitch the slices back together, align each one with the next,
color-code the wiring, and find the connections. This is harder than it might
seem. “If you make a single mistake, then all of the connections attached to
that wire are now incorrect,” Jain says.
“The ability to get this deep a reconstruction of any human
brain sample is an important advance,” says Seth Ament, a neuroscientist at the
University of Maryland. The map is “the closest to the ground truth that
we can get right now.” But he also cautions that it’s a single brain specimen
taken from a single individual.
The map, which is freely available at a web platform
called Neuroglancer,
is meant to be a resource other researchers can use to make their own
discoveries. “Now anybody who’s interested in studying the human cortex in this
level of detail can go into the data themselves. They can proofread certain
structures to make sure everything is correct, and then publish their own findings,”
Jain says. (The preprint has already been cited at least 136
times.)
The team has already identified some surprises. For example,
some of the long tendrils that carry signals from one neuron to the next formed
“whorls,” spots where they twirled around themselves. Axons typically form a
single synapse to transmit information to the next cell. The team identified
single axons that formed repeated connections—in some cases, 50 separate
synapses. Why that might be isn’t yet clear, but the strong bonds could help
facilitate very quick or strong reactions to certain stimuli, Jain says. “It’s
a very simple finding about the organization of the human cortex,” he says. But
“we didn’t know this before because we didn’t have maps at this resolution.”
The data set was full of surprises, says Jeff Lichtman, a
neuroscientist at Harvard University who helped lead the research. “There were
just so many things in it that were incompatible with what you would read in a
textbook.” The researchers may not have explanations for what they’re seeing,
but they have plenty of new questions: “That’s the way science moves
forward.”
Correction: Due to a transcription error, a quote from
Viren Jain referred to how the brain 'exports' memories. It has
been updated to reflect that he was speaking of how the brain 'stores'
memories.
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