Differential activation of the medial temporal lobe during item and associative memory across time.

Studies have shown that the hippocampus plays a crucial role in associative memory. One central issue is whether the involvement of the hippocampus in associative memory remains stable or declines with the passage of time. In the majority of studies, memory performance declines with delay, confounding attempts at interpreting differences in hippocampal activation over time. To address this issue, we tried to equate behavioral performance as much as possible across time for memory of items and associations separately. After encoding words and word pairs, participants were tested for item and associative memories at four time intervals: 20-min, 1-day, 1-week, and 1-month. The results revealed that MTL activation differed over time for associative and item memories. For associative memory, the activation of the anterior hippocampus decreased from 20-min to 1-day then remained stable, whereas in the posterior hippocampus, the activation was comparable for different time intervals when old pairs were correctly retrieved. The hippocampal activation also remained stable when recombined pairs were correctly rejected. As this condition controls for familiarity of the individual items, correct performance depends only on associative memory. For item memory, hippocampal activation declined progressively from 20-min to 1-week and remained stable afterwards. By contrast, the activation in the perirhinal/entorhinal cortex increased over time irrespective of item and associative memories. Drawing on Tulving's distinction between recollection and familiarity, we interpret this pattern of results in accordance with Trace Transformation Theory, which states that as memories are transformed with time and experience, the neural structures mediating item and associative memories will vary according to the underlying representations to which the memories have been transformed.