Friday, December 16, 2011

Brain Wiring a No-Brainer?

The brain appears to be wired more like the checkerboard streets of New York City than the curvy lanes of Columbia, Md., suggests a new brain imaging study. The most detailed images, to date, reveal a pervasive 3D grid structure with no diagonals, say scientists funded by the National Institutes of Health.

“Far from being just a tangle of wires, the brain’s connections turn out to be more like ribbon cables -- folding 2D sheets of parallel neuronal fibers that cross paths at right angles, like the warp and weft of a fabric,” explained Van Wedeen, M.D., of Massachusetts General Hospital (MGH), A.A. Martinos Center for Biomedical Imaging and the Harvard Medical School. “This grid structure is continuous and consistent at all scales and across humans and other primate species.”

Wedeen and colleagues report new evidence of the brain’s elegant simplicity March 30, 2012 in the journal Science. The study was funded, in part, by the NIH’s National Institute of Mental Health (NIMH), the Human Connectome Project of the NIH Blueprint for Neuroscience Research, and other NIH components.

“Getting a high resolution wiring diagram of our brains is a landmark in human neuroanatomy,” said NIMH Director Thomas R. Insel, M.D. “This new technology may reveal individual differences in brain connections that could aid diagnosis and treatment of brain disorders.”

Knowledge gained from the study helped shape design specifications for the most powerful brain scanner of its kind, which was installed at MGH’s Martinos Center last fall. The new Connectom diffusion magnetic resonance imaging (MRI) scanner can visualize the networks of crisscrossing fibers – by which different parts of the brain communicate with each other – in 10-fold higher detail than conventional scanners, said Wedeen.

“This one-of-a-kind instrument is bringing into sharper focus an astonishingly simple architecture that makes sense in light of how the brain grows,” he explained. “The wiring of the mature brain appears to mirror three primal pathways established in embryonic development.”

As the brain gets wired up in early development, its connections form along perpendicular pathways, running horizontally, vertically and transversely. This grid structure appears to guide connectivity like lane markers on a highway, which would limit options for growing nerve fibers to change direction during development. If they can turn in just four directions: left, right, up or down, this may enforce a more efficient, orderly way for the fibers to find their proper connections – and for the structure to adapt through evolution, suggest the researchers.

Obtaining detailed images of these pathways in human brain has long eluded researchers, in part, because the human cortex, or outer mantle, develops many folds, nooks and crannies that obscure the structure of its connections. Although studies using chemical tracers in neural tracts of animal brains yielded hints of a grid structure, such invasive techniques could not be used in humans.

Wedeen’s team is part of a Human Connectome Project Harvard/MGH-UCLA consortium that is optimizing MRI technology to more accurately to image the pathways. In diffusion imaging, the scanner detects movement of water inside the fibers to reveal their locations. A high resolution technique called diffusion spectrum imaging (DSI) makes it possible to see the different orientations of multiple fibers that cross at a single location – the key to seeing the grid structure ceus for social workers

In the current study, researchers performed DSI scans on postmortem brains of four types of monkeys – rhesus, owl, marmoset and galago – and in living humans. They saw the same 2D sheet structure containing parallel fibers crossing paths everywhere in all of the brains – even in local path neighborhoods. The grid structure of cortex pathways was continuous with those of lower brain structures, including memory and emotion centers. The more complex human and rhesus brains showed more differentiation between pathways than simpler species.

Among immediate implications, the findings suggest a simplifying framework for understanding the brain’s structure, pathways and connectivity.

The technology used in the current study was able to see only about 25 percent of the grid structure in human brain. It was only apparent in large central circuitry, not in outlying areas where the folding obscures it. But lessons learned were incorporated into the design of the newly installed Connectom scanner, which can see 75 percent of it, according to Wedeen.

Much as a telescope with a larger mirror or lens provides a clearer image, the new scanner markedly boosts resolving power by magnifying magnetic fields with magnetically stronger copper coils, called gradients. Gradients make it possible to vary the magnetic field and get a precise fix on locations in the brain. The Connectom scanner’s gradients are seven times stronger than those of conventional scanners. Scans that would have previously taken hours – and, thus would have been impractical with living human subjects – can now be performed in minutes.

“Before, we had just driving directions. Now, we have a map showing how all the highways and byways are interconnected,” said Wedeen. “Brain wiring is not like the wiring in your basement, where it just needs to connect the right endpoints. Rather, the grid is the language of the brain and wiring and re-wiring work by modifying it.”

Sunday, December 4, 2011

Friendly-to-a-Fault, Yet Tense: Personality Traits Traced in Brain

Scans Reveal How Genes Alter Circuit Hub to Shape Temperament – NIH Study

A personality profile marked by overly gregarious yet anxious behavior is rooted in abnormal development of a circuit hub buried deep in the front center of the brain, say scientists at the National Institutes of Health. They used three different types of brain imaging to pinpoint the suspect brain area in people with Williams syndrome, a rare genetic disorder characterized by these behaviors. Matching the scans to scores on a personality rating scale revealed that the more an individual with Williams syndrome showed these personality/temperament traits, the more abnormalities there were in the brain structure, called the insula CADC I & II Continuing Education

“Scans of the brain’s tissue composition, wiring, and activity produced converging evidence of genetically-caused abnormalities in the structure and function of the front part of the insula and in its connectivity to other brain areas in the circuit,” explained Karen Berman, M.D., of the NIH’s National Institute of Mental Health (NIMH).

Berman, Drs. Mbemda Jabbi, Shane Kippenhan, and colleagues, report on their imaging study in Williams syndrome online in the journal Proceedings of the National Academy of Sciences.

“This line of research offers insight into how genes help to shape brain circuitry that regulates complex behaviors – such as the way a person responds to others – and thus holds promise for unraveling brain mechanisms in other disorders of social behavior,” said NIMH Director Thomas R. Insel, M.D.

Williams syndrome is caused by the deletion of some 28 genes, many involved in brain development and behavior, in a particular section of chromosome 7. Among deficits characteristic of the syndrome are a lack of visual-spatial ability – such as is required to assemble a puzzle – and a tendency to be overly-friendly with people, while overly anxious about non-social matters, such as spiders or heights. Many people with the disorder are also mentally challenged and learning disabled, but some have normal IQs.

Previous imaging studies by the NIMH researchers found abnormal tracts of the neuronal fibers that conduct long-distance communications between brain regions -- likely resulting from neurons migrating to the wrong destinations during early development.

Evidence suggests that genes influence our temperament and the development of mental disorders via effects on brain circuits that regulate behavior. Yet direct demonstration of this in humans has proven elusive. Since the genetic basis of Williams syndrome is well known, it offers a unique opportunity to explore such effects with neuroimaging, reasoned the researchers.

Although the insula had not previously been studied in such detail in the disorder, it was known to be related to brain circuitry and certain behaviors, such as empathy, which is also highly prominent in the disorder. Berman and colleagues hypothesized that the insula’s anatomy, function and connebtivity would predict patients’ scores for Williams syndrome-associated traits on personality rating scales. Fourteen intellectually normal Williams syndrome participants and 23 healthy controls participated in the study.

Magnetic resonance imaging (MRI) revealed that patients had decreased gray matter – the brain’s working tissue – in the bottom front of the insula, which integrates mood and thinking. By contrast, they had increased gray matter in the top front part of the insula, which has been linked to social/emotional processes.

Diffusion tensor imaging, which by detecting the flow of water in nerve fibers can identify and measure the connections between brain areas, showed reduced white matter – the brain’s long-distance wiring – between thinking and emotion hubs.

Tracking radioactively-tagged water in order to measure brain blood flow at rest, via positron emission tomography (PET), exposed activity aberrations consistent with the MRI abnormalities. The PET scans also revealed altered functional coupling between the front of the insula and key structures involved in thinking, mood and fear processing. These structural and functional abnormalities in the front of the insula correlated with the Williams syndrome personality profile.

“Our findings illustrate how brain systems translate genetic vulnerability into behavioral traits,” explained Berman.

The severity of abnormalities in insula (red structure near bottom of brain) gray matter volume (left) and brain activity (right) predicted the extent of aberrant personality traits in Williams syndrome patients – as reflected in their scores (red dots) on personality rating scales (WSPP).

Source: Karen Berman, M.D., NIMH Clinical Brain Disorders Branch

Long distance connections, white matter, between the insula and other parts of the brain are aberrant in Williams syndrome. Neuronal fibers of normal controls (left) extend further than those of Williams syndrome patients (right). Picture shows diffusion tensor imaging data from each patient superimposed on anatomical MRI of the median patient.