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Director’s Blog: Brain’s Wiring Revealed in HD

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In the years after Francis Crick and James Watson described the double helical structure of DNA, both men became interested in the brain. While Watson searched for the genetics of schizophrenia, Crick became intrigued by consciousness and brain structure. In contrast to genetics, their adopted field of neuroscience proved far more challenging. In 1993, Crick and his colleague Ted Jones wrote of their frustration in an essay for Nature entitled “The Backwardness of Human Neuroanatomy.”  They noted that the rodent brain and monkey brain had been mapped, but “it is intolerable that we do not have this information for the human brain. Without it there is little hope of understanding how our brains work except in the crudest way.”

What a shame that neither Crick nor Jones lived to see the paper by Wedeen and colleagues in the current issue of Science – and the striking images coming from the new “Connectom” scanner! For the first time, we are seeing the connections of the human brain with the kind of detail and breadth that have been sorely lacking. The connectome, as this wiring diagram is called, provides a roadmap of the human brain. To be sure, there are few surprises in this new report – post-mortem studies of the human brain gave us most of the major pathways a century ago. What is new is a technology that will allow studies of the living, developing, adapting brain. And, importantly, the connectome will be based on lots of different brains. Just as the genome project taught us about the unexpected variation in human genetic sequence, the connectome project promises to reveal individual differences in brain wiring that may be markers for vulnerability or resilience for mental disorders.

While the pictures of the connectome are exciting, it is still only a roadmap, helpful for knowing where the freeways and side roads are, but not a reflection of the points of interest or inhabitants. A deep understanding of a city requires knowing who lives in the various neighborhoods and how people live in these neighborhoods. A functional connectome, a map that shows which brain neighborhoods are linked and what the various areas do, is being completed with functional magnetic resonance imaging (fMRI), a technique that describes how brain areas are synchronized and which circuits are critical for perception, motor control, and emotion.

The next challenge will be putting these various maps together. Will the functional connections align with the wiring diagram? Will there be meaningful differences between individuals? Will individual differences in brain align with individual differences in mind? All of these questions can now be addressed with these new powerful approaches. For the past decade we at NIMH have been saying that mental disorders can be addressed as brain disorders. The connectome gives us a new tool for studying mental disorders, one that may be as transformative as the EKG for heart disease and PET scans for cancer.

But we also need to manage expectations. As Watson and Crick discovered, the human brain has a complexity that is humbling even for the most intrepid and accomplished scientist. As Watson said in his book about the brain (Discovering the Brain), “The brain is the last and grandest biological frontier, the most complex thing we have yet discovered in the universe. It contains hundreds of billions of cells interlinked through trillions of connections. The brain boggles the mind.

diffusion tensor image of human brain’s connections

Curvature in this diffusion spectrum image of a whole human brain turns out to be folding of 2D sheets of parallel neuronal fibers that cross paths at right angles, say researchers. This picture came from the Connectom scanner, a new tool of the Human Connectome Project .
Source: Van Wedeen, M.D., Martinos Center and Dept. of Radiology, Massachusetts General Hospital and Harvard University Medical School

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Reference

Wedeen VJ, Rosene DL, Ruopeng W, Guangping D, Mortazavi F, Hagmann P, Kass JH, Tseng W-YI. The Geometric Structure of the Brain Fiber Pathways: A Continuous Orthogonal Grid. March 30, 2012 Science.