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Archive for the ‘Superior temporal cortex’ Category

morph_slicer_demoThe brain is a wonderfully weird and strange organ to behold.  Its twists and folds, magnificent, in and of themselves, are even moreso when we contemplate that the very emotional experience of such beauty is carried out within the very folds.  Now consider the possibility of integrating these beauteous structure/function relationships with human history – via the human genome – and ask yourself if this seems like fun.  If so, check out the recent paper, “Genetic and environmental influences on the size of specific brain regions in midlife: The VETSA MRI study” [doi:10.1016/j.neuroimage.2009.09.043].

Here the research team – members of the Biomedical Informatics research Network – have carried out the largest and most comprehensive known twin study of brain structure.  By performing structural brain imaging on 404 male twin pairs (important to note here that the field still awaits a comparable female study), the team examined the differences in identical (MZ) vs. fraternal (DZ) pair correlations of the structure of some 96 different brain regions.  The authors now provide an updated structural brain map showing what structures are more or less influenced by genes vs. environment. Some of the highlights from the paper are that genes accounted for about 70% of overall brain volume, while in the cortex, genes accounted for only about 45% of cortical thickness.  Much of the environmental effects were found to be non-shared, suggesting, as expected, that individual experience can have strong effects on brain structure.  The left and right putamen showed the highest additive genetic influence, while the cingulate and temporal cortices showed rather low additive genetic influences (below 50%).

If you would like to play around with a free brain structure visualization tool, check out Slicer 3D, which can be obtained from the BIRN homepage or directly here.  I had fun this morning digitally slicing and dicing grey matter from ventricles and blood vessels.

slicer

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A column of the cortex
Image by Ethan Hein via Flickr

Here’s a new addition to a rapidly growing list of findings for the valine-to-methionine substitution in the COMT gene (rs4680).  The paper, “Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents” by Shaw and colleagues at the NIMH [doi:10.1038/mp.2008.121] finds that when genotype was used as a regressor for cortical thickness measures in children (8-14 years of age) significant associations were found in the right inferior frontal gyrus and the right superior/middle temporal gyrus (in both areas, the met/met group had thicker cortex).  The team notes that the findings in the frontal cortex were expected – as many others have found associations of COMT with this brain area using other imaging modalities.  However, the temporal lobe finds are something new.  No speculations on the mechanisms/implications are provided by the researchers on this new finding, but known interconnectivities of these two brain regions exist – perhaps supporting aspects of language, memory and/or other cognitive processes?

Perhaps the findings provide a clue to an important role that genes may play in the development of cognitive function.

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Day 191 - Stick it Out

Image by lintmachine via Flickr

Like “Joe the Plumber” (whose real name is Samuel), CNTNAP2 (whose real name is CASPR2) has achieved a bit of fame lately.  While recently appearing almost everywhere (here, here, here) except FOX News, CNTNAP2 (not Joe the Plumber) is apparently a transcriptional target of the infamous FOXP2 “language gene” – so says Sonja C. Vernes & colleagues [doi: 10.1056/NEJMoa0802828] who precipitated DNA-protein complexes using anti-FOXP2 antibodies from a cell line transiently expressing FOXP2. The team later evaluated measures of expressive and receptive language abilities and nonsense-word repetition and found that a series of snps – most significantly rs17236239 – were associated with performance of children from a consortium of families at risk for language impairment.  This adds to several previous reports of CNTNAP2 and risk for autism, a disorder where language ability is severely impaired.

So what’s all the fuss ? How can something so insignificant (rs17236239 not Joe the Plumber) stir up so much trouble ?  Well, as reported in a previous post, the expression of CNTNAP2 in the developing superior temporal cortex may be a relevant clue since this brain region is activated by language tasks.  Also, this gene encodes a rather massive protein which (as reported by Coman et al.,) seems to participate in the establishment of myelination and “nodes” that permit rapid neural transmission and long-range coordination across neural structures in the brain. Interestingly, this gene shows evidence for recent positive selection in humans (as posted on here and here) although the newly derived G-allele at rs17236239 seems to be the allele that is causing the language difficulties.  My own 23andMe profile shows a middling A/G here which makes it slightly hard to recall and repeat “Samuel Wurzelbacher”.

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raining words; in a moment
Image by pfv. via Flickr

The acquisition of language in humans remains a complex and fascinating mystery from both a neuro- and evolutionary-biological perspective. Attempts to identify genetic regulators of neural processes that are involved in language acquisition have the potential to shed light, not only on the natural history of homo sapiens, but also, to help understand the complex neurodevelopmental disorder, Autism, often associated with profound language impairments. So, it is very exciting to read, “Genome-wide analyses of human perisylvian cerebral cortical patterning” by Abrahams et al., (DOI) who examined human gene expression in frontal vs. superior temporal cortex at a developmental period where neurogenesis and neuronal migration are particularly active. The authors went looking for differential gene expression during a critical developmental time point and in a critical brain region – since the superior temporal cortex is an area that is reliably activated by linguistic tasks as well as social cognition tasks. According to the article, a total of 345 differentially expressed genes were identified, with 61 enriched and 284 down-regulated in superior temporal cortex across two microarray platforms, with 13 genes identified by both microarray array platforms. One of the genes identified is LDB1, a regulator of the asymmetrically expressed LIM domain-only 4 (LMO4) a known mediator of calcium-dependent transcription in cortical neurons and known to regulate thalamocortical connectivity. Another gene, CNTNAP2, a member of the neurexin transmembrane superfamily of proteins that mediate cellular interactions in the nervous system has been previously associated with autism. Both of these genes seem to have important developmental roles and should provide access to the fine-scale wiring that occurs during the development of neural networks involved in language.

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