brain region, in association with a specific cognitive task, is lower than what is observed in younger animals. An intervention study is planned, whereby a genetically engineered virus is packaged with recombinant DNA that codes for the expression of the down-regulated receptor, along with genes that will enable temporal control of expression and spatial restriction of expression to the specific cells in question. The virus is injected into the relevant brain region, whereupon it infects cells and results in the transgenes being inserted into the host DNA. Gene expression is subsequently activated to produce the receptor protein, which is thus up-regulated to levels present in younger animals. At this point, one needs an assay of neuronal activity to determine whether the manipulation has had the desired functional effect. fMRI provides such a dependent measure, which can be compared with the preintervention state. Moreover, when obtained in conjunction with a behavioral index of cognitive function, the MR signal can be used as a basis for identifying the neuronal substrates of any cognitive gain. An intervention approach of this sort will soon be possible using new molecular genetic tools, and will clearly have broad applicability in conjunction with fMRI.
In sum, the great richness of fMRI in nonhuman primates—for aging research and for neuroscience generally—lies in the fact that the method can be applied in conjunction with many other techniques that cannot be used for research on human subjects. The "whole" that we stand to gain from such conjunctions is surely far greater than what can be learned from each technique on its own.
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