Prefrontal and hippocampal contributions to the generation and binding of semantic associations during successful encoding

The ability to form and bind associations between items is an important aspect of successful memory formation. We hypothesize that, during encoding, the left inferior frontal gyrus (IFG) supports generation of associations between items and the hippocampus then binds these associations. This study examined the parametric responses of these regions to varying amounts of generative and relational processing during successful encoding (i.e., for subsequently recognized items) ' Encoding involved presentation of word triads varying in the number of semantic associations among them (none, one or all); participants judged how many associations were present in each triad. Thus, triads with fewer associations had higher generative load while triads with more associations had higher relational load. Participants later completed a forced-choice recognition test for encoding triads. Successful encoding relative to a control task resulted in activation of bilateral IFG and left hippocampus, and the hippocampus also exhibited a significant subsequent memory effect (hits > misses). Linear parametric analyses revealed that generative load modulated activity in bilateral IFG while relational load correlated with activity in left hippocampus. Although univariate analyses distinguished IFG and hippocampal contributions to the generative and relational stages of encoding, respectively, effective connectivity between these regions did not differ according to condition. Furthermore, this analysis revealed that the left IFG played a pivotal role in coordinating associative encoding processes. Our findings illustrate that modulation of components in a memory network can be independent of patterns of mutual connectivity among those components in mediating successful encoding. (c) 2006 Elsevier Inc. All rights reserved.