Understanding the Brain's Connectivity on Cellular and Mechanistic Levels

In 1993, some researchers decried: "It is intolerable that we do not have a knowledge of the connectivity of the human brain." Do we know more now?

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A pivotal paper was this opinion piece in Nature magazine by Francis Crick & Jones in 1993 in which they decried the fact that we have no knowledge of connectional anatomy in the human. And over on the right they showed what connectional anatomy might look like. And that's David Van Essen and Felleman's classic depiction of the Rhesus monkey visual system, and they said, "This is what we need in humans." Well, I don't think they went nearly far enough in their ambitions. This image on the right is only one part of a brain, and it's compiled from hundreds of monkey brains. And cannot possibly be duplicated in a human because, of course, it was an invasive procedure. You had to inject, and then kill the monkey, and slice up its brain and so on. So there's no way to imagine any human counterpart to that. But moreover you only learn about one connection or a couple of connections per experiment. You don't understand they're a 3-dimensional relationship. So you are orders of magnitude away from a diagnostic technique. In a diagnostic technique you would want to see everything there is to see in a human brain all at once. Just once you would like to know the anatomy of the brain assembled 3-dimensionally. How does it assemble? But secondly, you'd like to see how it varies from individual to individual. But thirdly, you'd like to do it while they're still alive. In some ways it's less than they wanted because they really wanted cellular connectivity. And we're not getting that. We're getting an average, which has possible errors and approximations. It's an indirect measure. On the other hand, this indirect measure is made for the entire brain in human subjects in vivo. So those are significant practical advantages. So obviously the challenge is to understand the relationship between this approximation that we have on the one hand, and the cellular level connectivity on the other hand-- the mechanistic level.
Posted on BrainLine March 18, 2013.

About the author: Van Wedeen. MD

Van Wedeen, MD is associate professor in Radiology at Harvard Medical School, assistant neuroscientist at Massachusetts General Hospital, and director of Connectomics at Martinos Center, Department of Radiology, Massachusetts General Hospital.

Van Wedeen

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