Temporo-prefrontal coordination increases when semantic associations are strongly encoded.

Relational association of disparate semantic concepts can strengthen encoding of episodes. Previous research has shown that the left medial temporal lobe (MTL) and the left prefrontal cortex (PFC) are the primary brain regions activated during both verbal encoding and the association of disparate semantic concepts. In the current functional magnetic resonance imaging (fMRI) study, our goal was to compare the coordinated response of the left MTL and left PFC when disparate semantic associations are strongly encoded compared to when they are weakly encoded. To achieve this goal, subjects were scanned while creating sentences based on a presented pair of words, and were asked to free-recall these sentences at a later time. Half the word pairs were semantically unrelated, and half were semantically related. Analysis of relatedness activations (unrelated-related contrast) suggested that the PFC was active whether or not the items were free-recalled, and increased activation of the MTL was required to promote encoding. Analyses of coordination of relatedness activations comparing free-recalled items to not free-recalled items showed an increase in left MTL-left PFC coordination for relatedness activations on free-recalled items. These results suggest that formation of relational semantic associations that lead to strongly encoded episodes requires increased coordination of the left MTL-left PFC neural pathway.