The medial temporal lobe and the left inferior prefrontal cortex jointly support interference resolution in verbal working memory.

During working memory retrieval, proactive interference (PI) can be induced by semantic similarity and episodic familiarity. Here, we used fMRI to test hypotheses about the role of the left inferior frontal gyrus (LIFG) and the medial temporal lobe (MTL) regions in successful resolution of PI. Participants studied six-word lists and responded to a recognition probe after a short distracter period. We induced semantic PI by using study lists containing words within the same semantic category (e.g., animals). We also measured PI induced by recent study, which should increase episodic familiarity, by comparing recent negative probes (lures studied in previous trial) to distant negative probes (lures that had not been presented within a block). Resolving both types of PI resulted in enhanced activation in LIFG and MTL regions. We propose that the LIFG and the MTL support successful resolution of interference via controlled retrieval processes that serve to recover detailed episodic (e.g., list-specific or source) information: Specifically, the data suggest that BOLD activation in the LIFG reflects the deployment of controlled retrieval operations, regardless of whether the retrieval attempt succeeds in recovering the target information, whereas MTL activation specifically reflects access to relevant episodic information that serves to successfully resolve PI.