The new Allen Brain Atlas combines neuroimaging and detailed cell studies to create the most detailed ever map of the brain.
One of the biggest hurdles neuroscientists face today is the incredible complexity of the organ they work with. Because so many different parts come together to make it work (and because so many of those parts are so tiny) there isn’t an exact template of where each piece starts and where it ends. But now, after a five-year-long effort, Ed Lein and his colleagues from the Allen Institute for Brain Science in Seattle have put together a comprehensive, open-access digital atlas of the human brain — think of it as the Google map of the brain, complete with markers and street-view.
“Essentially what we were trying to do is to create a new reference standard for a very fine anatomical structural map of the complete human brain,” says Ph.D. and Lead Investigator at the Allen Institute for Brain Science Ed Lein.
“It may seem a little bit odd, but actually we are a bit lacking in types of basic reference materials for mapping the human brain that we have in other organisms like mouse or like monkey, and that is in large part because of the enormous size and complexity of the human brain.”
The project was based on a single healthy postmortem brain of a 34-year-old woman. The team started by taking full scans of the organ in magnetic resonance and diffusion weighted imaging to capture the overall structure and the way fibers connect inside the brain. Then, it was time to look inside. The brain was sliced up into 2,716 thin sections for cellular analysis. Parts of these sheets of brain were dyed with Nissl stain, and their cell architecture was examined. The team then used two other stains to selectively label certain aspects of the brain, such as structural elements of cells, fibers in the white matter, and specific types of neurons.
Based on the Nissl-stained slides, the team cataloged 862 distinct brain structures, finding some novel subregions of the thalamus and amygdala and two other structures that have previously only been described in non-human primates.
When the team put the overall high-resolution data together with the detailed, cellular-level structure of each area, they annotated the atlas with the brain structure they identified. Lein explains that the atlas is available online so people can “navigate it, and move from the macro level all the way right into the cellular level.”
He says that the atlas will become an invaluable tool for neuroscientists to use as common starting material — a set of well-defined areas on which they can later add more levels of annotation based on the criteria they need.
“To understand the human brain, we need to have a detailed description of its underlying structure,” says Lein.
One brain to map them all
Mapping the human brain has long been a major goal of neuroscientists who are trying to make heads and tails of how it works, what its parts are and what these parts actually do. Last year, researchers from the Human Connectome Project released a detailed brain map based on multiple MRI measurements recorded from 210 healthy patients. Lein and his colleagues chose to concentrate their efforts on only one brain to go into a lot more detail with their work.
“Because of the labor intensiveness of doing this, it always lives in the scale of a single brain,” Lein says, “and you really go to town in trying to understand everything you can about that one individual.”
But going in-depth on a single specimen also has its drawbacks. Human Connectome Project researcher Matthew Glasser thinks that the Allan Brain Atlas is “impressive” particularly on a neuroanatomical level, but points out that it might be hard to generalize the findings to the whole human race.
“The thing that’s a challenge is relating a single brain like this that’s very intensively studied to other brains,” Glasser says.
But the thing to remember is that before these two datasets became available, the best reference material we’ve had was put together in 1909, when German anatomist Korbinian Brodmann used Nissl staining to create a cellular-scale brain map. Most brain-mapping efforts to date are still based on Brodmann’s work — hopefully, the new Allen Brain Atlas will speed up such efforts in the future.
“There simply hasn’t been a complete map of the human brain as a reference piece of material for anyone studying any part of the brain,” Lein says, “and this is a completely essential part of doing research.”
The full paper “Comprehensive cellular-resolution atlas of the adult human brain” has been published in The Journal of Comparative Neurology.