Map of brain at cellular level should aid Alzheimer research

In what’s being called a landmark development for neuroscience, researchers have created a 3-D digital reconstruction of a complete human brain that for the first time shows the organ’s complex anatomy at the cellular level.

Dubbed BigBrain, the computer-based map of the brain provides a spatial resolution of 20 microns — smaller than the width of a single strand of human hair and 50 times more refined than existing reference brains available for scientific study.

“This allows us a completely new level of insight into the brain’s organization,” said co-developer Alan Evans of the Montreal Neurological Institute at McGill University.

“What this allows us is to further examine the interaction between different brain regions, the organization of the brain and how it observes behaviour — how it underpins how our brains work and how we function as human beings,” said Evans, director of the Montreal Consortium for Brain Imaging Research.

“So we have raised the level of insight … beyond what was possible at the turn of the 20th century. This dataset will revolutionize our ability to understand internal brain organization.”

To construct BigBrain, scientists took the brain of an unidentified 65-year-old woman, who had died with no evidence of neurological disease. The brain was embedded in paraffin wax and cut into more than 7,400 slices using a special large-scale tool called a microtome.

The 20-micrometre-thick sections — likened to small pieces of plastic sandwich wrap — were mounted on slides and stained to detect cell structures. The slices were then digitized with a high-resolution scanner so researchers could construct the high-resolution 3-D brain model. Collecting the data took about 1,000 hours.

The result is an online map that provides extremely fine details of the brain’s microstructure at the cellular level. Previously available reference brains did not probe further than the macroscopic, or visible, components of the brain.

While not every cell can be seen, the map for the first time allows deeper analysis of the brain’s architecture and distribution of neurons and other cells in sub-layers of the brain, something that wasn’t possible before, said Dr. Katrin Amunts, head of the Institute for Brain Research at Heinrich Heine University in Dusseldorf, Germany.

The new reference brain, which is part of the European Human Brain Project, “redefines traditional maps from the beginning of the 20th century,” she said. “The famous cytoarchitectural atlases of the early 1900s were simplified drawings of a brain and were based on pure visual analysis of cellular organization patterns.”

The finely detailed anatomical resolution of BigBrain will allow scientists to gain insights into the neurobiological basis of cognition, language, emotions and other processes, the authors report in Thursday’s issue of the journal Science.

“You can look at practically all the areas in the brain,” said co-author Dr. Karl Zilles, senior professor at Germany’s Julich Aachen Research Alliance. “For instance, when you are interested in a common neurodegenerative disorder like Alzheimer’s disease, you have the first-ever brain model where you can look into details of the hippocampus, which is the brain region extremely important for memory.

“You can look into brain regions which are connected with the hippocampus and play a major role in this disease, but you can also study how many cells you need to build up a cortical unit model in 3-D.

“It is a common basis for scientific discussions because everybody can work with the brain model and speak about the same basic findings,” he said. “If you take one brain here and another brain there, then you start to compare differences, but what we need for answering principal and basic questions in neuroscience is to have a common structure, which is the basis for all our discussions.”

Evans said staff at the Montreal Neurological Institute (MNI), where the brain slices were digitized and compiled using advanced software, are already using BigBrain.

Specialists such as neuroanatomists and neurosurgeons at the MNI are “absolutely ecstatic” over their ability to explore structures of the brain, he said, explaining that an MRI can provide only a fraction of the detail exhibited by BigBrain.

“So the surgeons are all running in and out of the room trying to get at the data on the very, very big screen that we have on a wall.”

Evans said BigBrain is like a scaffold on which the visual data has been built, and new information can be added as more is revealed about the microscopic structures and intricate functions of the brain’s various regions.

The scientists are already in discussions with other research groups, including those at the Allen Institute for Brain Science in Seattle, which has compiled a number of its own specialized brain “atlases.”

“We’ve been working and speaking with scientists from the institute precisely about this issue of integrating data that they are collecting into the space of the BigBrain,” said Evans.

“So we are already on this case, and we are very excited about the possibility of … data integration into the BigBrain space.”