The new Allen Brain Atlas combines neuroimaging and tissue staining to offer an unprecedented level of resolution.
Ed Lein and colleagues at the Allen Institute for Brain Science in Seattle have created a comprehensive, open-access digital atlas of the human brain, which was published this week in The Journal of Comparative Neurology.
“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 Lein, the principal investigator on the project. “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, which spanned five years, focused on a single healthy postmortem brain from a 34-year-old woman. The researchers started with the big picture: They did a complete scan of the brain using two imaging techniques (magnetic resonance imaging and diffusion weighted imaging), which allowed them to capture both overall brain structure and the connectivity of brain fibers.
Next the researchers took the brain and sliced it into 2,716 very thin sections for fine-scale, cellular analysis. They stained a portion of the sections with a traditional Nissl stain to gather information about general cell architecture. They then used two other stains to selectively label certain aspects of the brain, including structural elements of cells, fibers in the white matter, and specific types of neurons.
The researchers also took a subset of the Nissl-stained slides and used them to catalogue 862 different brain structures, including novel subregions of the thalamus and the amygdala, and two other structures that previously had only been described in non-human primates.
The key step in creating a complete brain atlas was combining broad-scale, high-resolution brain imaging data with detailed cellular-level mapping, which the researchers then annotated with the brain structures they identified. The entire map is available online. Lein explains that the atlas can be accessed via a portal, where people can “navigate it, and move from the macro level all the way right into the cellular level.”
Lein thinks the atlas may be a particularly valuable tool for neuroscientists who can use it as a common starting point and add layers of annotation based on their own criteria for dividing up the brain.
Human brain mapping has long been a goal of neuroscientists, who, along with the rest of us, are eager to figure out how exactly this essential mass of tissue inside our skulls should be divided up, and what the different areas actually do. In 1909, German anatomist Korbinian Brodmann used the same Nissl method of staining to create a cellular-scale brain map, which formed the basis for many brain-mapping efforts to follow.
Researchers from the Human Connectome Project released their own detailed brain map earlier this year. Using a broad-scale approach, they compiled brain images from multiple MRI measurements performed on 210 healthy adults.
For Lein and his colleagues, however, concentrating their efforts on only one brain allowed them 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. ”
Matthew Glasser of Washington University School of Medicine, who was part of the Human Connectome Project effort but was not involved with the present study, calls the brain atlas “impressive,” particularly on a neuroanatomical level, but points out that it may be difficult to generalize the information from one individual. “The thing that's a challenge is relating a single brain like this that's very intensively studied to other brains,” he says.
Nevertheless, the effort marks a substantial advance in our understanding of brain anatomy. “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.”