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Biomedicine

First Detailed Map of the Human Cortex

A new imaging technique reveals previously hidden brain structures, including the central hub.

The first high-resolution map of the human cortical network reveals that the brain has its own version of Grand Central Station, a central hub that is structurally connected to many other parts of the brain. Scientists generated the map using a new type of brain imaging known as diffusion imaging. The technique maps the largely inaccessible tangle of the brain’s white matter–the long, thin fibers that ferry nerve signals between cells. Scientists hope that using the noninvasive method to study neural connections in people with Alzheimer’s, schizophrenia, and autism will shed light on how changes in brain architecture are linked to these complex diseases.

Cortical core: Scientists used a new type of brain imaging called diffusion spectrum imaging, along with mathematical analysis, to build a map of the cortical architecture of the human brain, shown here. The blue lines represent neural fibers connecting different parts of the brain. To make the map easier to understand, only the strongest connections are shown. Letters indicate anatomic subregions of the brain.

“The fact that such a core exists gives rise to many questions we can now ask about it,” says Olaf Sporns, a neuroscientist at Indiana University, in Bloomington, and senior author of the study, published this week in PLoS Biology. “What goes on there? And how is it involved in passing messages between different parts of the brain?”

Conventional imaging techniques, such as structural magnetic resonance imaging (MRI), reveal major anatomical features of the brain. But in humans, the brain’s finer architecture–the neural projections that connect its different parts–has, until recently, remained hidden. “The brain we’ve been looking at with conventional MRI or CT scans all these years is not the real brain,” says Van Wedeen, a neuroscientist at Massachusetts General Hospital, in Boston, who was also involved in the study. “We’re just seeing a shadow of its surfaces.”

Diffusion imaging is a new twist on MRI that uses magnetic resonance signals to track the movement of water molecules in the brain.In gray matter, water tends to diffuse multidirectionally. But in white matter, it diffuses along the length of neural wires, called axons, and scientists can use these diffusion measurements to map the fibers. The newest incarnation of diffusion imaging, called diffusion spectrum imaging, allows scientists to perform a very difficult feat: determining the direction of overlapping nerve fibers. “That’s very important for noninvasive mapping of brain connectivity,” says Wedeen, who developed the technique.

Wedeen and his collaborators used diffusion spectrum imaging to image the brains of five healthy volunteers, generating a wiring map of the entire cortex. To reveal the core of the network, Sporns used a mathematical technique to repeatedly prune away the connection points with the fewest links. “If you do it gradually, you end up with a set of nodes remaining that are highly interconnected,” he says.

The most highly connected node, which Sporns dubbed the core, is located at the back of the head, in parts of the brain known as the posterior medial and parietal cerebral cortex. The node lies on the shortest path between many different parts of the neural network. “It’s highly connected amongst itself, but also highly central with respect to the rest of the brain,” says Sporns. “Network studies in other fields, from the Internet to protein interaction networks, suggest that these kinds of highly connected nodes tend to be very important for determining what the network does as a whole.”

Previous functional brain-imaging studies have also highlighted this region: it’s one of the most metabolically active parts of the brain, particularly when people are cognitively at rest, meaning that they are awake and alert but not engaging in any particular task. “People refer to this as the resting state, daydreaming, or self-referential processing,” says Sporns. As part of the new study, Sporns and his colleagues also used functional magnetic resonance imaging to measure blood flow to different parts of the brain. They found that it correlated with the level of white-matter connectivity in the individual subjects.

The researchers want to use the imaging technique to look at clinical conditions such as schizophrenia, autism, and Alzheimer’s disease, all of which have been linked to disturbances in brain architecture. “We would like to know where the disturbances are and whether we can understand something about the clinical condition based on the connectivity,” says Sporns.

However, scientists will likely need to improve the technique before they can use it to study patients. Getting enough detail to make the maps requires longer scanning times than are typical in clinical settings. “Right now, this probably isn’t practical to look at large populations of patients,” says Marco Catani, a clinical neuroscientist at the Institute of Psychiatry, in London, who was not involved in the study.

The researchers are already trying to refine their approach, generating new methods to improve the signal-to-noise ratio of the data they collect. They consider their new map just the first of many drafts. “We’re not yet at the level where we can sequence the brain with the same kind of precision with which we could sequence the genome,” says Wedeen. “Only when we see the organs of the brain–a few hundred areas of gray matter with distinct functions, and the connections between them–will we have an image of the brain that is comparable to what we expect the structure to be.”

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