The folds, creases and intricate internal structures that make up the human brain are being revealed in unprecedented detail. A new three-dimensional map called BigBrain is the most detailed ever constructed, and should lead to a more accurate picture of how the brain's different regions function and interact.
Until now, the precise placement of the neurons that make up our brain circuitry has been difficult to map, largely because the human brain's surface is covered with folds and creases. Slicing a brain exposes only two dimensions, so it is often unclear where and how the cells within these folds are organised in three-dimensional space.
To make the new map, Katrin Amunts of the Jülich Research Centre in Germany and her colleagues embedded a 65-year old woman's brain in wax, sliced it into more than 7400 sections each 20 micrometres thick – one-fifth of the width of a human hair – and made digital images of the slices, also at a resolution of 20 micrometres.
Reassembling these images into a full 3D model of the brain was no easy task. It required 1000 hours on a supercomputer. But because the images' resolution was so high, the computer was able to determine the 3D shape of each fold correctly, even if the slice had been cut at an angle.
"It's a tour de force that has never been achieved before," says Arthur Toga of the University of California, Los Angeles. The model's resolution is 50 times higher than that of previous maps, allowing it to make out individual cell bodies – although not all of the projections that connect one cell to another. It bridges a gap, Toga says, between low-resolution images from brain scans of living people and microscopic images of the connections between individual nerve cells.
Amunts's group plans to post BigBrain online as a template for other researchers to use and integrate with other findings. For instance, by superimposing maps of gene activity, it may be possible to work out which cells are performing particular functions. It may also serve as a useful reference for the BRAIN initiative championed by US president Barack Obama, which aims to map all of the brain's activity. "You can't map function unless you can relate it to structure," says Toga.
Van Wedeen of Harvard University, who has argued that the brain is based on an underlying 3D grid, hopes the map will reveal similarly unexpected patterns and structure. "There's a tremendous amount we still don't know," he says.
By making similar maps of further brains, it should also be possible to study natural variability in brain structure, and look for abnormalities linked to specific neurological diseases. Amunts is already well on the way to reconstructing a second brain – which should go faster now that her group has trail-blazed its method.
Meanwhile, Jacopo Annese of the University of California, San Diego, is in the midst of constructing maps based on fewer, thicker slices, but imaging each with a resolution of just 0.5 micrometres. This should reveal the connections between individual cells.
Annese's group, called The Brain Observatory, recently sliced the brain of a person who had suffered from epilepsy and who had lost his long-term memory after surgery. The team is now constructing digital models of sections from this brain and those from 60 other people, including some who had been living with various psychiatric disorders.