NSF – It was previously thought the inside of the brain resembled the assembly of a bowl of spaghetti noodles. Researchers and scientists, funded by the National Science Foundation, have now discovered that a more uniformed grid-like pattern makes up the connections of the brain. 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.
They are 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.
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
Van Wedeen and team discovered that the pathways in the top of the brain are all organized like woven sheets with the fibers running in two directions in the sheets and in a third direction perpendicular to the sheets. These sheets all stack together so that the entire connectivity of the brain follows three precisely defined directions.
The directions of the pathways of the brain were previously difficult to determine because in embryological life the pathways run in simple directions but become very bent and folded as the brain matures into an adult and more information and skills are learned. The surface of the adult brain appears more folded and the three directions become increasingly curved and thus difficult to view definitively.
Path neighborhood in rat left ventricular myocardium (stereo pair), comprised circumferential fibers
The structure of the brain as a product of morphogenesis is difficult to reconcile with the observed complexity of cerebral connectivity. We therefore analyzed relationships of adjacency and crossing between cerebral fiber pathways in four nonhuman primate species and in humans by using diffusion magnetic resonance imaging. The cerebral fiber pathways formed a rectilinear three-dimensional grid continuous with the three principal axes of development. Cortico-cortical pathways formed parallel sheets of interwoven paths in the longitudinal and medio-lateral axes, in which major pathways were local condensations. Cross-species homology was strong and showed emergence of complex gyral connectivity by continuous elaboration of this grid structure. This architecture naturally supports functional spatio-temporal coherence, developmental path-finding, and incremental rewiring with correlated adaptation of structure and function in cerebral plasticity and evolution.
Credit: NSF and Harvard University for Video
This detail from a DSI scan shows a fabric-like 3-D grid structure of connections in monkey brain. Credit: Van Wedeen, M.D., Martinos Center and Dept. of Radiology, Massachusetts General Hospital and Harvard University Medical SchoolM
A mosaic of hundreds of interconnected and microscopically identifiable areas in the human cerebral cortex controls cognition, perception, and behavior. Each area covers up to 40 cm2 of the cortical surface and consists of up to 750 million nerve cells. The architecture—the spatial distribution, density, size, and shape of nerve cells and their processes—varies between different cortical areas. Nerve cells are interconnected within each area and with other brain regions and the spinal cord via fiber tracts, synapses, transmitters, modulators, and receptors. This incredible structural complexity underlies the functional segregation in the cerebral cortex. The ultimate goal—to understand the driving forces and organizational principles of the human brain beyond the cellular and functional details—remains a challenge. Reports by Chen et al. and Wedeen et al. on pages 1634 and 1628 of this issue, respectively, accept this challenge by analyzing the genetic topography of the cortex and the spatial course of fiber pathways in the brain. The studies find unifying hierarchical and geometric rules behind the organizational details.
Surface area of the cerebral cortex is a highly heritable trait, yet little is known about genetic influences on regional cortical differentiation in humans. Using a data-driven, fuzzy clustering technique with magnetic resonance imaging data from 406 twins, we parceled cortical surface area into genetic subdivisions, creating a human brain atlas based solely on genetically informative data. Boundaries of the genetic divisions corresponded largely to meaningful structural and functional regions; however, the divisions represented previously undescribed phenotypes different from conventional (non–genetically based) parcellation systems. The genetic organization of cortical area was hierarchical, modular, and predominantly bilaterally symmetric across hemispheres. We also found that the results were consistent with human-specific regions being subdivisions of previously described, genetically based lobar regionalization patterns.
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