Corticolimbic interactions associated with performance on a short-term memory task are modified by age.

Aging has been associated with a decline in memory abilities dependent on hippocampal processing. We investigated whether the functional interactions between the hippocampus and related cortical areas were modified by age. Young and old subjects' brain activity was measured using positron emission tomography (PET) while they performed a short-term memory task (delayed visual discrimination) in which they determined which of two successively presented sine-wave gratings had the highest spatial frequency. Behavioral performance was equal for the two groups. Partial least squares (PLS) analysis of PET images identified a hippocampal voxel whose activity was similarly correlated with performance across groups. Using this voxel as a seed, a second PLS analysis identified cortical regions functionally connected to the hippocampus. Quantification of the neural interactions with structural equation modeling suggested that a different hippocampal network supported performance in the elderly. Unlike the neural network engaged by the young, which included prefrontal cortex Brodmann's area (BA) 10, fusiform gyrus, and posterior cingulate gyrus, the network recruited by the old included more anterior areas, i.e., dorsolateral prefrontal cortex (BA 9/46), middle cingulate gyrus, and caudate nucleus. Recruitment of a distinct corticolimbic network for visual memory in the elderly suggests that age-related neurobiological deterioration not only results in focal changes but also in the modification of large-scale network operations.