Tuesday, September 22, 2020

The Astonishing Connectome


Gray matter isn't the big story. Connection—the connectome—is the astonishing feature of the brain.



 We hear a good deal about the gray matter (the neurons) in the brain. They are often considered synonymous with thinking. For a long time, it was believed that the white matter did not do very much and its signals were generally excluded from brain mapping studies as noise. But that has all changed in recent years:

You might think that the brain is mostly gray matter, as it certainly looks that way, but in actuality there is more white matter in the brain. White matter is the infrastructure of the brain and includes the long nerve axons and their protective layer of fat, called myelin. Gray matter, on the other hand, is composed of the neurons themselves. Scientists have long thought that white matter didn’t play an active role in the brain, but new research has shown that this is untrue and that white matter actively affects both how the brain learns and how it dysfunctions.

From the little we understand about our hundred-billion neuron brains, connection is everything. Thus the Human Connectome Project (HCP), launched 2009, seeks to understand some of those connections better by surveying the brain imaging data from hundreds of people.

The challenge? The unthinkably large number of connections:

As of yet, scientists have only identified one connectome: that of a nematode (Caenorhabditis elegans). Its modest nervous system consists of 300 neurons. In the 1970s and 1980s, a team of researchers traced a map of its 7,000 interneural connections. The name for that map, as we mentioned before, is the connectome. Obviously, human beings are much more complex, with more than 100 billion neurons and 10 thousand times more connections.

The surprise? The brain is quite orderly, not the haphazard accumulations of aeons of evolution that the researchers expected:

LONDON’S STREETS ARE a mess. Roads bend sharply, end abruptly, and meet each other at unlikely angles. Intuitively, you might think that the cells of our brain are arranged in a similarly haphazard pattern, forming connections in random places and angles. But a new study suggests that our mental circuitry is more like Manhattan’s organised grid than London’s chaotic tangle. It consists of sheets of fibres that intersect at right angles, with no diagonals anywhere to be seen.

Van Wedeen from Massachusetts General Hospital, who led the study, says that his results came as a complete shock. “I was expecting it to be a pure mess,” he says. Instead, he found a regular criss-cross pattern like the interlocking fibres of a piece of cloth. …

Wedeen’s maps may not reveal all the details about the brain’s network, but it does show how that network is structured. “If you look at brain connections in an adult human, it’s really a massive puzzle how something so complex can emerge,” says Behrens. “If we can establish any sort of organisation, we get a clue about how these things grow. If it obeys some rules, you could start to work out how it follows those rules. You have something to hang onto.”

At Medical Daily,we learn more about the project itself:

The project comprises 36 investigators, including biologists, physicians, physicists, and computer scientists, at 11 institutions across the nation. The primary centers of research are USC’s Laboratory of Neuroimaging, Massachusetts General Hospital’s Martinos Center, Washington University’s Van Essen Lab, and the University of Minnesota’s Center for Magnetic Resonance Research.

The project was carried out in two phases. During Phase I, which spanned the years 2010 through 2012, research teams designed the project’s 16 major components. During Phase II, which ranged from 2012 through this past summer, the various scientists performed the actual work of gathering data. More importantly, however, during the most recent phase investigators made their datasets publicly available at regular intervals so that scientists around the world could begin to use them in their own projects.

But the surprise factor has not abated:

What’s been discovered so far?

Many surprises. Scientists have been amazed to see that, instead of chaos, the connecting fibers are organized into an orderly 3D grid, where axons run up and down and left and right, minus any diagonals or tangles. Science magazine compares the brain’s 3D layout to New York City, with its streets running in two directions and buildings’ elevators running up and down. Strangely, in flat areas of the grid, the fibers overlap at precise 90 degree angles and weave together much like a fabric, the scientists say.


While there is much more to learn—the project was described to MedicalDaily as “a 30,000-foot fly-by view”—new findings amount to teasing out the innumerable details of a fundamentally orderly structure. But trying to completely understand the brain would be like trying to completely understand New York City.

Help with understanding schizophrenia?

Because the brain is an unexpectedly orderly structure, close examination of the connectome can help medical researchers see what is going wrong when our brains don’t co-operate with us. For example, there is some evidence that schizophrenia has a basis in faulty brain connections:

Researchers have consistently found patterns of abnormally high or low connectivity in the brains of schizophrenic patients. So delusions, hallucinations, and depression-like symptoms might not be a result of one region acting strangely—they could instead arise from flawed communication among regions.

Brains of persons who suffer from schizophrenia also lack “small-worldness.” That’s the quality by which most brain nodes cluster into thickly connected modules in which one node is a hub that connects long range across the network. It’s somewhat like a local club where one member volunteers for the duty of communicating with the central organization and the local media. But what if communications are less frequent and more haphazard?

But while the healthy brain is a small-world network, the schizophrenic brain is measurably less so—it can still be organized into modules, but those modules aren’t as densely connected. If small-worldness helps the brain undertake a variety of processes effectively and efficiently, its lack in the schizophrenic brain could someday help to explain the disease’s symptoms.

By itself, that finding doesn’t point to a cure. But as knowledge of unexpected patterns accumulates, a clearer picture of the problem is forming. Down the road, that ever more precise picture will suggest possible treatments.

Materialism may keep us from important insights. Computational neuroscientist Sebastian Seung, a rising star in the study of the connectome (connectomics), announced at TED, “I am my connectome.” No, he isn’t his connectome or his brain either. Or his brain and body. The unexpected orderly structure of the brain suggests a bigger picture. And it is within that structure that answers will be found.