Parallel Engagement of Regions Associated with Encoding and Later Retrieval Forms Durable Memories.

UNLABELLED: The fate of a memory is partly determined at initial encoding. However, the behavioral consequences of memory formation are often tested only once and shortly after learning, which leaves the neuronal predictors for the formation of durable memories largely unknown. Here, we hypothesized that durable memory formation (as opposed to weak or no memory formation) is reflected through increased activation in the medial temporal lobes and prefrontal cortex, and more consistent processing (i.e., stronger pattern similarity) across encoding material. Thirty-four human subjects studied unique picture-location associations while undergoing fMRI and performed a cued recall test immediately after study as well as 48 h later. Associative memories were defined as "weak" if they were retrieved during the immediate test only. Conversely, "durable" memories persisted also after 48 h. The posterior cingulate cortex showed increased pattern similarity during successful memory formation, independent of the eventual durability. For durable memory encoding, we found increased activation in medial and inferior temporal, prefrontal, and parietal regions. This was accompanied by stronger pattern similarity in lateral prefrontal and parietal regions, as well as in anterior and posterior midline structures that were also engaged during later memory retrieval. Thus, we show that pattern similarity, or consistent processing, in the posterior cingulate cortex predicts associative memory formation at encoding. If this is paralleled by additional activation increases in regions typically related to encoding, and by consistent processing in regions involved in later retrieval, formed memories appear durable for at least 48 h. SIGNIFICANCE STATEMENT: Successful memory formation is typically associated with increased neuronal activation in medial temporal and prefrontal regions at encoding, but memory is often assessed only once and shortly after study. Here, we addressed memory durability, and investigated the neuronal underpinnings of encoding for associations remembered over a longer period of time, less long, or immediately forgotten. We showed that durable memory formation is dependent on increased activation in the hippocampus and neocortical regions related to encoding, and on consistent processing of associative memory traces in midline structures that are involved in later memory retrieval. These findings highlight how durable memories are formed.