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.
Key words: aging; functional connectivity; hippocampus; partial least squares; short-term memory; structural equation modeling; visual memory; plasticityThere is consensus about the critical role of the hippocampus in declarative memory (Milner, 1978;Squire and Zola-Morgan, 1991;Eichenbaum et al., 1996;Tulving and Markowitsch, 1998). There is also little doubt that memory capacities dependent on hippocampal processing decline with age. Until recently, memory decay in the elderly was thought to originate in deficient hippocampal processing associated with its anatomical deterioration. However, neuroanatomical studies demonstrating no changes in hippocampal cell number and size across age have questioned this old hypothesis (Sullivan et al., 1995;Rapp and Gallagher, 1996;Morrison and Hof, 1997). Recently, Smith et al. (1999) have shown that agerelated structural degeneration occurs in subcortical neuronal populations of the basal forebrain, which constitute a major cholinergic input to neocortex. Thus, loss of critical subcortical afferents, together with age-related molecular changes in receptor number and dendritic arborization (Morrison and Hof, 1997), may act to disrupt hippocampal physiology (Barnes, 1979;Barnes and McNaughton, 1980;Bach et al., 1999) and consequently, memory performance Gallagher and Rapp, 1997; Tanila et al., 1997a,b). Given the current scenario, examination of functional interactions between the hippocampus and its afferents is critical for understanding the basis of age-rela...