Saturday, May 12, 2012

Train lines though the mind

New papers about gross brain anatomy find a few interesting things.

A pair of recent articles gave new insights into the organization of the white and gray matter of the brain, respectively. They represent the forefront of trying to learn in a holistic way how the brain naturally develops and organizes, and provide a few intriguing results.

First off, the grey matter. A large research group sought to define how much different people's brains vary genetically, and how this variation maps on the brain surface. That is, do whole areas like the frontal cortex co-vary between people as a coherently expanding or contracting surface, or do smaller sub-regions have more independence to grow and shrink, depending on genetic background? Does brain anatomy vary at all depending on genetics?

They did this using that warhorse of human genetics- identical vs faternal twins, in this case drawn from a registry of Vietnam-era twins registered for the US military draft, who were all male and now middle-aged. They put pairs into MRI scanners and used some sophisticated math to abstract the shapes of everyone's brain, after which they could measure how they all compared in some detail.

One would think that, since the brain remains functionally quite plastic in adulthood, volume-based differences between people might be influenced by experience as much as genetics. Or more. But in most of the gray matter (outside the hippocampus and a few other areas), there is no cell division in adulthood, so while those neurons can re-wire and re-purpose themselves to new tasks, (itself quite a mysterious process), the overall morphology is set by early adulthood, changing only by way of decline and senility. Speaking of which ... where are my reading glasses?

The researchers find that genetic relationship corresponds to broad volume concordance in a jig-saw like map that divides the brain surface into twelve large regions. These regions mostly match regions that have already been recognized by other anatomical and functional maps, like for instance, area six, the superior temporal cortex, important for speech and hearing.



The interesting findings are that there are genetic variations in brain construction that are consistent and can be detected at all, and also that they conveniently resolve down to large-scale anatomical structures that have for the most part been long recognized for their functional differentiation from neighboring areas, for instance when tested with electrode probes in live patients. This of course leads to the question of just how different consciousness and other mental capabilities are between people, (though the differences here are tiny- on the border of detectability). And whether perhaps genetic structural variations correlate with genetically-driven variations in temperament, personality, and other mental characteristics / abilities. Phrenology might be making a high-tech, if minor, comeback!

The other paper dealt with deeper issues, which is to say, the white matter wiring pattern beneath the gray matter surfaces of the brain- how this pattern compares between different species, and how simple rules of development might result in the complex resulting pattern.

This novel method of MRI that isolates myelinated nerve pathways is truly remarkable (although fiber tracts have been studied in other ways for a long time). I only wish we had some analogous chemical/mathematical/technical magic to see live cancers in similar isolation. Anyhow, they visualize the long-range myelinated nerve bundles in the brains of humans, rhesus and owl monkeys, marmosets (a new world monkey), and galagos (a relatively primitive old-world primate). Importantly, they also group the pathways by an algorithm depending on extended proximity, which allows them to automatically color-code them into sheets of nerves that are structurally and developmentally coherent. You can see that this leads to a striking map of major internal brain pathways.



Aside from the artificially colored beauty of all these pathways, one can note a few things. Unfortunately, the colors of homologous pathways are not kept the same across species, but there are clear homologies, like of the sagital stratum which conducts visual signals to the visual cortex at the back of the brain. To the untrained eye, the tangles seem almost chaotic, but the researchers put them into a developmental context where the brain is the developmentally deformed result of what originates as a sheet of cells, expanded into three dimensions. Unfortunately they don't detail graphically quite exactly what they are talking about in this respect.

Secondly, there seem to be coherent sheets of nerves, supporting, as does the paper above, a natural structural division of white matter into wiring with plainly differentiated functions., One might presume also the possibility of natural genetic variation in these structures as well, incidentally.

Thirdly, the most interesting observation is that each sheet of nerve fibers meets others at roughly right angles. You can see this theme of 3-D criss-crossing immediately in the images, and as the researchers note, "geometrically, this configuration is highly exceptional". From a statistical standpoint, if the only rule were that each nerve had to find its target, winding pell-mell through the volume of the brain, you would see spaghetti.



What this means is that these observations are consistent with models by which the brain develops by relatively simple rules where bundles/sheets of related nerve fibers travel in tight groups as they migrate through the brain in development, and make rather simple cardinal coordinate decisions whenever they meet other such bundles, typically growing right through them. There is a substantial history, in the molecular biology of neural pathfinding, of nerves making such simple directional decisions during development, so this study shows the same procedure writ large, as the rule more or less throughout the brain.

The researchers summarize: "We have found that the fiber pathways of the forebrain are organized as a highly curved 3D grid derived from the principal axes of development. This structure has a natural interpretation. By the Frobenius theorem, any three families of curves in 3d mutually cross in sheets if and only if they represent the gradients of three corresponding scalar functions. Accordingly, we hypothesize that the pathways of the brain follow a base-plan established by the three chemotactic gradients of early embryogenesis. Thus, the pathways of the mature brain presents an image of these three primordial gradients, plastically deformed by development."

So, sort of like the grids of wire bundles you see in server racks and similar computer installations, or schematic train line maps, neurological development generates grids of myelinated (fast) fiber pathways to efficiently conduct data all over the brain.

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