Explaining the encoding/retrieval flip: memory-related deactivations and activations in the posteromedial cortex

The posteromedial cortex (PMC) is strongly linked to episodic memory and age-related memory deficits. The PMC shows deactivations during a variety of demanding cognitive tasks as compared to passive baseline conditions and has been associated with the default-mode of the brain. Interestingly, the PMC exhibits opposite levels of functional MRI activity during encoding (learning) and retrieval (remembering), a pattern dubbed the encoding/retrieval flip (E/R-flip). Yet, the exact role of the PMC in memory function has remained unclear. This review discusses the possible neurofunctional and clinical significance of the E/R-flip pattern. Regarding neurofunctional relevance, we will review four hypotheses on PMC function: (1) the internal orienting account, (2) the self-referential processing account, (3) the reallocation account, and (4) the bottom-up attention account. None of these accounts seem to provide a complete explanation for the E/R-flip pattern in PMC. Regarding clinical relevance, we review work on aging and Alzheimer's disease, indicating that amyloid deposits within PMC, years before clinical memory deficits become apparent. High amyloid burden within PMC is associated with detrimental influences on memory encoding, in particular, the attenuation of beneficial PMC deactivations. Finally, we discuss functional subdivisions within PMC that help to provide a more precise picture of the variety of signals observed within PMC. Collective data from anatomical, task-related fMRI and resting-state studies all indicate that the PMC is composed of three main regions, the precuneus, retrosplenial, and posterior cingulate cortex, each with a distinct function. We will conclude with a summary of the findings and provide directions for future research.