The medial temporal lobe (MTL) and the prefrontal cortex (PFC) are known to be critical structures for human memory processes. Furthermore, it has been suggested that they are part of a memory network. Although memory-modulated interaction between PFC and MTL has been observed at the hemodynamic level, it remains unclear what the neuronal process is that mediates the communication between these 2 areas. Experiments in rodents suggest that field oscillations in the theta band (4-8 Hz) facilitate PFC-MTL interaction. No such evidence has been reported in humans. To address this problem, cortical electrical activity from MTL, PFC, and lateral temporal lobe was recorded from implanted electrode grids in 3 epilepsy patients performing a verbal free recall task. The data were analyzed using a parametric spectral method to obtain estimates of power, coherence, and Granger causality. A task-modulated increase in coherence values between PFC and MTL was seen during free recall as opposed to a baseline condition. Concurrently, the number of coherent PFC-MTL site pairs was significantly increased during recall. Granger causality analysis further revealed that the increased coherence is a consequence of higher bidirectional information flow between the 2 regions, with a generally greater driving from MTL to PFC, namely, (MTL-->PFC) > (PFC-->MTL).

The means by which VNS improves retention is probably related to the increased activity in the nucleus of the tractus solitarius and the locus coeruleus-central adrenergic system that activates the amygdala and increases long-term potentiation in the hippocampus.

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Our results suggest that when using semantic encoding, older normal subjects may be aided by anticholinesterase treatment. However, this treatment does not improve recall of superficially encoded words.