Building a Vision of the Networks of the Brain

by Tom Valeo

March 2, 2010

Think of the current view of the human brain as a Google map of the United States, with states and major cities clearly identified. Click on the “zoom” button again and again, and the Interstate Highway system comes into view, followed by major state roadways, secondary roads, and eventually local streets. You see not just the important destinations, but also the connections that link them into a dynamic, interactive unit.

The “zoom” button for brain scientists is a relatively new technique called diffusion tensor imaging (DTI), which reveals for the first time the fiber tracts that link far-flung regions of the living brain, enabling them to communicate with each other. Instead of focusing on separate “cities”—the visual cortex, the auditory cortex, the hippocampus, and so on—scientists are beginning to see how these brain regions exchange information, transforming humble electrochemical impulses into what we experience as consciousness.

This view of the brain, according to neuroscientist Olaf Sporns, bears an uncanny resemblance to a network diagram. And most networks rely on busy hubs.

On a map of air routes, for example, Chicago is a conspicuous hub, receiving and dispatching large numbers of airplanes that provide an efficient path for passengers traveling from one city to another. And anyone who has been trapped at O’Hare Airport in a snowstorm knows that a problem at a hub can create massive disruptions throughout the network.

“This is purely metaphorical, but it could be that the brain has hubs, and when hubs are disturbed or damaged, that has a severe effect on what the brain does,” says Sporns, a professor of psychological and brain sciences at Indiana University. “If that turns out to be correct, it would help our understanding of many brain disorders.”

Sporns calls the map of brain circuits the connectome, a word he introduced in 2005 when he proposed, in a paper in PLoS Computational Biology, a strategy for plotting those vital circuits. He and Ed Bullmore of the University of Cambridge reviewed the current understanding of brain networks in a recent issue of Nature Reviews Neuroscience.

The word connectome plays off of genome, and Sporns believes that identifying neural networks will transform brain science just as plotting the human genome has transformed biology. “The connectome won’t answer every question,” says Sporns, “but it might allow us to ask the right questions.”

The National Institutes of Health apparently agrees with Sporns’ assessment. Last summer it announced $30 million in funding over five years for the Human Connectome Project, dedicated to mapping the neural networks of the brain.

Peeks at intelligence, schizophrenia

Although still in its infancy, connectomics has started to produce tantalizing insights into some of the brain’s greatest mysteries.

Intelligence, for example, appears to depend more on robust connections among various brain regions than on the size and vigor of the regions themselves. This has long been suspected, since those connections, known as axons, comprise so much of the brain’s volume. But researchers in the Netherlands provided evidence in the June 2009  Journal of Neuroscience that intelligent people do indeed have brain networks that are more efficiently organized. By measuring the number of steps needed for a signal to travel from one part of the brain to another, they found that “the networks of the most intelligent people showed the shortest functional travel distances,” says lead author Martijn P. van den Heuvel, of the Rudolf Magnus Institute of Neuroscience in the Netherlands, in a printed summary of the findings presented at a recent meeting of the Society for Neuroscience. Smarter brains did not show more connections, but these shorter distances showed they transported information among their connections more efficiently.

“Our findings indicate that intelligence is likely related to how directly, and therefore to how efficiently, high order regions have access to information from other regions, and to how efficiently this information can be integrated globally across the entire brain network,” says van den Heuvel.

Researchers Richard J. Haier of the University of California, Irvine, and Rex E. Jung of The Mind Institute in Albuquerque, have used DTI and other imaging techniques to provide evidence supporting their P-FIT model of intelligence, which links IQ to the integrity of the axonal tracts that connect the parietal region near the back of the brain with the prefrontal cortex (P-FIT stands for parieto-frontal integration theory). They reported the work in the March-April 2009 issue of Intelligence.

Conversely, other researchers have found a correlation between mental retardation and a lack of white matter integrity in various brain regions including the corpus callosum, which links the left and right hemispheres, as reported in NeuroImage in May 2008.

Based on the emerging understanding of brain networks, some researchers suspect that schizophrenia, one of the most puzzling brain disorders, may result from faulty wiring. This is not a new theory. Karl Wernicke first proposed the idea in 1906, and in 1911 Paul Bleuler, an early supporter of Sigmund Freud, coined the word “schizophrenia” (from the Greek words for “split” and “mind”) to suggest a lack of connection among various brain regions.

But only recently have brain scans, especially DTI, started to reveal solid evidence of abnormal brain connections in people with schizophrenia. One recent paper, for example, found altered connectivity, especially in the prefrontal cortex, which might help explain the flat emotions, lack of motivation, and other “negative” symptoms of the disease. And a group at the University of California, Los Angeles, recently produced the first evidence of white matter problems in young people at high risk of developing schizophrenia, suggesting that the disease begins in the white matter before symptoms appear.

Autism also appears to result, at least in part, from faulty brain wiring. DTI research reported at the annual meeting of the International Society for Autism Research last spring found evidence of compromised brain connections in people diagnosed with autism.

Age and injury might break wiring

Problems with the human connectome also may play a role in Alzheimer’s disease, according to Harvard researcher Randy Buckner and colleagues. They have found that the “default network,” which becomes active when a person is daydreaming and not focused on a specific task, coincides with the pattern of degeneration found in people with Alzheimer’s.

Buckner and colleagues have found that the default network contains several of the “hubs” that Sporns believes to be an essential part of the connectome. Research suggesting that high activity in a brain region accelerates degeneration makes Buckner suspect that these busy hubs may be predisposed to the breakdown that leads to Alzheimer’s. Their research was reported in February 2009 in the Journal of Neuroscience.

Another study used DTI to detect subtle damage to brain connections—damage that appears to herald the onset of Alzheimer’s long before memory problems begin.

Sporns suspects that concussions and other forms of brain injury may also damage the connectome. “No matter where you lesion the brain, you will see that changes ripple through the entire network,” he says. “If you lesion some localized part of the brain, regions far removed might be perturbed.”

Learning from his work

Sporns has just finished writing a book called Networks of the Brain, which will present an up-to-the-moment report on current understanding of those linkages that comprise the human connectome. The book will be released in fall 2010.

“Writing it was a good exercise in uncovering the central role of connectivity in virtually all aspects of brain function,” he says. “The brain makes more sense when you think of it not as a trillion independent moving parts, but as an integrated system. In neuroscience we’ve been trying to focus on elements. That’s essential, but we also have to put the pieces back together. We’re making a big effort to get at the brain’s connectivity because it will lay a foundation for a new understanding of how the brain works.”