Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice

We have developed a Variant of functional magnetic resonance imaging (fMRI) designed to be sensitive to static neuronal function. This method is based on resting instead of dynamic changes in oxygen-dependent signal and there fore allows for a spatial resolution that can detect signal from different hippocampal subregions in human subjects as well as in mice. We found that hippocampal signal was significantly diminished in elderly subjects with me mory decline compared to age-matched controls, and different subjects showe d dysfunction in different subregions. Among healthy elders, signal intensi ty from the subiculum was correlated selectively with memory performance. T his method does not require an activation task; it can be used in anestheti zed normal and in genetically modified and cognitively impaired mice. In mi ce the signal was found to be sufficiently sensitive to detect functional c hanges in the absence of underlying anatomical changes.