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Posts Tagged ‘Functional magnetic resonance imaging’

Varian 4T fMRI, part of the Brain Imaging Cent...Image via Wikipedia Among complex biological datasets, human genomic and functional imaging of the brain are right up there with the most fearsome wild & hairy beasts. Initial attempts to begin to tame the pair of these beasts by cross-relating the two forms of data have employed highly focused, hypothesis-testing strategies – for good reason – any exploratory association study would require a prohibitively large subject population. Liu and colleagues, in their paper, “Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA(DOI) provide a new statistical approach to parsing out meaningful neuroanatomical and genetic components from such complex datasets. The authors record brain activity data while subjects attempt to pick out auditory oddball sounds (beep-beep-beep-beep-beep-boop-beep-beep-). As reported, an analysis of the MRI data and a SNP array consisting of 384 SNPs from 222 genes revealed 10 SNPs that were associated with specific patterns of brain activity. Several SNPs were identified (rs3087454 and rs1355920 are located in the nicotinic acetylcholine receptor-7 (CHRNA7) subunit, rs7520974 is located in the muscarininc acetylcholine receptor-3 (CHRM3) subunit while rs885834 is located in the choline acetyl transferase (CHAT) gene) that would explain the known role of acetylcholine in parietal lobe function, a brain region commonly activated in auditory oddball perception tasks. The method – far beyond this author’s sophistication – nevertheless, seems to output data that is well supported by other forms of converging evidence.

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Holiday time is full of all things delicious and fattening. Should I have a little chocolate now, or wait till later and have a bigger dessert ? Of course, this is not a real forced choice (in my case, the answer too often seems – alas – “I’ll have both!”), but there are many times in life when we are forced to decide between ‘a little now’ or ‘more later’. Sometimes, its clear that the extra $20 in your pocket now would be better utilized later on, after a few years of compound interest. Other times, its not so clear. Consider the recent ruling by the Equal Employment Opportunity Commission, which allows employers to drop retirees’ health coverage once they turn 65 and become eligible for Medicare. Do I save my resources now to provide for my geezerdom healthcare spending, or do I enjoy (spend) my resources now while I’m young and able ? How do I make these decisions ? How does my life experience and genome interact to influence the brain systems that support these computations ? Boettiger and company provide some insight to these questions in their paper, “Immediate Reward Bias in Humans: Fronto-Parietal Networks and a Role for the Catechol-O-Methyltransferase 158Val/Val Genotype(DOI). The authors utilize an assay that measures a subject’s preference for rewards now or later and use functional brain imaging to seek out brain regions where activity is correlated to preferences for immediate rewards. Dopamine rich brain regions such as the posterior parietal cortex, dorsal prefrontal cortex and rostral parahippocampal gyrus showed (+) correlations while the lateral orbitofrontal cortex showed a (-) correlation. Variation in the dopaminergic enzyme COMT at the rs165688 SNP also showed a correlation with preferences for immediate reward as well as with brain activation. The authors’ results suggest that improving one’s ability to weigh long-term outcomes is a likely therapeutic avenue for helping impulsive folks (like me) optimize our resource allocation. I have not yet had my genome deCODEd or Google-ed, but strongly suspect I am a valine/valine homozygote.

Indeed it seems I am a GG (Valine/Valine) at this site according to 23andMe !

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Daniel Weinberger and company have a new installment in-press at Biological Psychiatry in their epic program to untangle the genetic basis of schizophrenia – “Heritability of Brain Morphology Related to Schizophrenia: A Large-Scale Automated Magnetic Resonance Imaging Segmentation Study.” Like all complex illness, schizophrenia is regulated by a variety of environmental sources (perinatal complications, stress & substance abuse are a few) and equally regulated by heritable factors. Although several specific genes for schizophrenia have been painstakingly identified, the genes are expressed widely throughout the brain – making it difficult to pinpoint where in the brain the gene interacts with the environment to exert its detrimental effects. To solve this problem, Weinberger and colleagues pioneered a method known as imaging-genetics where they look at how individual genetic differences correlate with differences in brain structure or functional activity (if you ever have a chance to volunteer for an fMRI brain imaging study – go for it – it’ll be one of the top 10 weirdest experiences of your life). In their latest report, the team pioneers a new “fully-automated whole brain segmentation” technique to show that the genetic factors that put individuals at risk may be functioning vis-a-vis the hippocampus and neocortex. This narrows the search space a lot! and is a major step forward in beginning to localize where in the brain the genetic risk originates.

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