What Does Human Brain Mapping Actually Tell Us?

Alice G. Walton, Contributor



PHARMA & HEALTHCARE

6/21/2013 @ 2:04PM



BigBrain, Courtesy of Amunts et al 2013

Google “brain” right now and you’ll find a mountain of news stories on a development known as the BigBrain project, which came out just yesterday: Researchers in Europe and Canada have just mapped the human brain with a precision that’s so strikingly detailed, that it’s unprecedented in humans – and it’s in 3D. The team has devised a way to cut the brain into 20 micrometer-thick sections – far slimmer than the chunky 1 mm sections that have been available with magnetic resonance – dye them, scan them, and reconstruct the slices into a 3D “atlas” of the human brain. But while the research is impressive by any count, and it will certainly gives us some clues into brain cell function and anatomy, there’s a limit to what it can tell us.

To accomplish the mission, the team used the donated brain of a 65-year old woman. It was preserved in formalin and then set in paraffin before slicing. The sections were mounted on glass slides and stained. Then came the scanning prep.

“After this we had over 7400 histological sections,” says author Katrin Amunts. “And a large number of wooden boxes in the lab to hold them!” She and her team used a flatbed scanner to scan the slices – a process, says Amunts, that took about 1,000 hours alone. Part of the process was the removal of all the artifacts of slicing – folds, ruptures, and other miscellaneous blips.

The 3D image of the brain was formed by reconstructing the slices, making what is essentially a cell-by-cell computer image or “atlas” of the brain. The data take up a mind-boggling terabyte of space.

So what information does brain mapping actually offer? It will certainly give us a better idea of where one region ends and the next begins, for a closer understanding of behavior-brain correspondence. It will also allow researchers to start making simulations, perhaps making it possible to “see” what happens in various disease states, say, in an Alzheimer’s- or Parkinson’s afflicted brain over time. “Researchers can take these images,” says Amunts, “and measure surfaces, thicknesses of cortical layers. It provides precise anatomical measures, and lets us make comparisons to in vivo imaging.”

She adds that this brain essentially becomes a new gold standard in the field. “We have a new reference brain,” says Amunts. “It can help us address questions and data coming from neuroscience about things like receptor distribution, microanatomy. Before this, the data were so scattered, we haven’t been able to compare it very effectively.” Plus, the resolution from MRI scans is much poorer – a clumsy 1-mm thickness, which is “not good enough to address questions about microstructure,” adds Amunts.

In terms of the person-to-person brain differences that are inevitable, Amunts says, “This is true. And we’ve actually started second brain, to account for some of these. We’re aware of intersubject variability. But the first brain has all the areas that you need.” She says her team probably won’t do more than a few brains in total, given the massive time commitment each requires.

And BigBrain will almost certainly have some major clinical implications, giving doctors a hand in neurosurgery and in placing electrodes during procedures like deep brain stimulation (DBS).

What the project doesn’t do is tell us a whole lot about anything else – those “deeper” questions that we’re all dying understand. In this way, the headlines touting BigBrain’s ability to work such magic as to “unlock the secrets of the mind” and that kind of thing may not to so accurate.

In fact, in a well-timed New York Times editorial this week, David Brooks makes the important point that the brain is not, after all, the mind, and as much as we’d like to think we’re getting closer to grasping human consciousness and thought with imaging studies, we’re just not. The “neurocentrism,” he says, that we’re so attached to is actually not serving us so well at all. In his words, “An important task these days is to harvest the exciting gains made by science and data while understanding the limits of science and data. The next time somebody tells you what a brain scan says, be a little skeptical. The brain is not the mind.”

When asked about the limits of the 3D brain atlas, Amunts says that though it doesn’t answer all questions, ultimately, basic neuroscience is critical for what it can offer us. “I’m a physician by training. I want to know why the region in the language area is involved in language. You have to understand brain first.” Her past work has mapped out the architecture of the brain, and, she says, the specificity can be dazzling. “And now we can look at everything in the same brain. If you only do small bit, you don’t have the full truth. But now we can analyze the whole brain.”

So this is on many levels a big accomplishment for Europe’s Human Brain Project, which has the not unlike our own BRAIN initiative. But there are limits to what it can tell us, and it only gives a peek at what’s actually going on in our heads. There’s much more work to be done, and a staggering number of questions that still need answers.

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