Effects of healthy aging on hippocampal and rhinal memory functions: an event-related fMRI study

Abstract

Event-related functional magnetic resonance imaging was used to study the effects of healthy aging on hippocampal and rhinal memory functions. Memory for past events can be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an event is old or new without the recovery of contextual details (familiarity). There is evidence that recollection is more dependent on hippocampus, whereas familiarity is more dependent on the rhinal cortex, and that healthy aging has greater effects on recollection than on familiarity. However, little evidence is available about the neural correlates of these effects. Here, we isolated activity associated with recollection and familiarity by distinguishing between linear and quasi-exponential "perceived oldness" functions derived from recognition confidence levels. The main finding was a double dissociation within the medial temporal lobes between recollection-related activity in hippocampus, which was reduced by aging, and familiarity-related activity in rhinal cortex, which was increased by aging. In addition, age dissociations were found within parietal and posterior midline regions. Finally, aging reduced functional connectivity within a hippocampal-retrosplenial/parietotemporal network but increased connectivity within a rhinal-frontal network. These findings indicate that older adults compensate for hippocampal deficits by relying more on rhinal cortex, possibly through a top-down frontal modulation. This finding has important clinical implications because early Alzheimer's disease impairs both hippocampus and rhinal cortex.

Figure 1

(A) Young and older adults were selected in rank order based on recognition accuracy in the scanner (d-prime). (B) ROCs in young and older adults. The flatter shape and greater asymmetry of the ROC in young compared with older adults indicate a greater contribution of recollection in the former group.

Figure 2

The effects of aging yielded a double dissociation between 2 MTL subregions: whereas recollection-related (exponential) activity in the hippocampus was attenuated by aging, familiarity-related (linear) activity in the rhinal cortex was enhanced by aging.

Figure 3

Differential effects of aging on recollection-related (exponential) and familiarity-related (linear) activity in different subregions within left parietal and the posterior midline regions. Within the left parietal region, aging attenuated recollection-related parietotemporal activity but not familiarity-related parietooccipital activity. Within the posterior midline region, aging attenuated recollection-related retrosplenial activity but not familiarity-related dorsal posterior cingulate activity.

Figure 4

Correlation analyses using individual trial activity showed an age-related increase in connectivity within a rhinal-frontal network (A, B) coupled with an age-related decrease in connectivity within a hippocampal-retrosplenial/parietotemporal network (C, D). Group comparisons were based on 2-sample tests at P < 0.05 on the individual correlation maps, inclusively masked with the relevant main effects at P < 0.001 (e.g., young > old, inclusively masked with young). The bar graphs indicate effect sizes of the individual trial correlations on the group level.