Reviews and perspectivesExplaining the encoding/retrieval flip: Memory-related deactivations and activations in the posteromedial cortex
Highlights
► Posteromedial cortex (PMC) deactivates when Encoding and activates when Retrieving. ► Pre-clinical markers of Alzheimer's are linked to PMC changes and the E/R-flip. ► Four neurocognitive accounts are discussed that can possibly explain the E/R-flip. ► Future research on PMC function requires consideration of its functional subregions.
Introduction
The posteromedial cortex (PMC) is strongly associated with episodic memory and considered a central node of the default-mode (Buckner et al., 2008, Raichle et al., 2001). The default-mode network (DMN) involves a set of strongly connected regions that in functional neuroimaging studies tends to be activated during rest but deactivated during demanding cognitive tasks (Mazoyer et al., 2001, McKiernan et al., 2003, Shulman et al., 1997). According to the default-mode hypothesis, these deactivations arise, because PMC and other DMN regions support cognitive processes that normally occur during rest, but must be temporarily shut down when available resources are needed for active task performance (Raichle et al., 2001). Interestingly, successful learning of events (episodic encoding) has been associated with reduced activity in the PMC, whereas successful retrieval of events (episodic retrieval) has been associated with increased activity in the same region (e.g. Buckner et al., 1996, Daselaar et al., 2004, Hayama et al., 2012, Kim, 2011, Otten and Rugg, 2001, Shrager et al., 2008, Wagner et al., 1998, Wagner et al., 2005). These opposing effects, which have been dubbed the encoding/retrieval flip (E/R-flip), were originally reported by Daselaar et al. (2009) who observed this pattern not across participants in separate encoding and retrieval studies, but within the same study and within the same participants for a variety of stimuli and memory paradigms. Since then, the E/R-flip pattern has been replicated in several other studies (Gilbert, Armbruster, & Panagiotidi, 2011; Huijbers et al., 2009, Huijbers et al., 2011; Kim, Daselaar, & Cabeza, 2010; Vannini, O'Brien, O'Keefe, Pihlajamaki, Laviolette, & Sperling, 2011). Yet, despite the robustness of the E/R-flip, the functional significance of this pattern and the role of the PMC in memory still remain unclear.
This review aims to clarify the relation between the function of the PMC and the E/R-flip pattern, and includes three sections. Section 2 reviews studies that found the E/R-flip pattern and discusses how the E/R-flip may lead to competition between encoding and retrieval processes. Section 2.3 discusses the relevance of the E/R-flip for clinical studies of aging and Alzheimer's disease and provides a direct link between PMC deactivations during encoding and memory-decline. Section 3 focuses on four different hypotheses that could potentially explain the E/R-flip pattern in the PMC. Section 4 of our review discusses anatomical, functional, and connectivity findings indicating three functionally distinct subregions within PMC; the precuneus (Pcun), posterior cingulate cortex (PCC), and retrosplenial cortex (RsC). Distinguishing between these subregions should help to further clarify the role of PMC in memory function. The review ends with a concluding section and directions for future research.
Section snippets
Converging evidence for the encoding/retrieval flip
The most powerful method for identifying brain regions associated with successful memory encoding processes using fMRI is known as the subsequent memory paradigm. In this paradigm, encoding trials are back-sorted based on whether they are subsequently remembered (hit) or forgotten (miss). There have been numerous fMRI studies using this paradigm, which have generally found greater activity for encoding hits than misses, or a positive encoding success effect, in the medial temporal lobe (MTL), a
Theoretical accounts
The clinical research reviewed in the previous section suggests a link between PMC integrity, the E/R-flip pattern, and episodic memory. However, these findings do not explain the E/R-flip in terms of underlying cognitive processes. Four prevailing theories could potentially explain the E/R-flip: (1) the internal orienting account, (2) the self-referential processing account, (3) the reallocation account and, (4) the bottom-up attention account. Below, we discuss evidence in favor of, and
Functional subdivisions of PMC
One critical issue when interpreting fMRI results regarding PMC is that there is considerable evidence indicating functional subdivisions within PMC. Thus, simply considering these different areas as a single PMC region with one unitary function can hinder our understanding of the PMC. As noted at the beginning of this review, three major regions can be roughly discriminated within PMC: RsC, Pcun, and PCC.
The E/R-flip has been reported most consistently within PCC and Pcun (e.g. Daselaar et
Conclusions
The PMC reliably shows opposing levels of activation during encoding and retrieval, the E/R-flip pattern, and this can lead to a competition between encoding and retrieval states. In terms of clinical relevance, age-related pathology, specifically amyloid deposition within the PMC, has detrimental effects on the E/R-flip. Thus, the E/R-flip is an interesting candidate for tracking longitudinal changes in episodic memory during pre-clinical stages of Alzheimer's disease (Sperling et al., 2011).
Acknowledgments
This work was supported by the European Molecular Biology Organization: ALTF 318-2011 [W.H.], the Amsterdam Brain Imaging Platform [W.H, S.D.], the Marie Curie Fellowship: FP7-PEOPLE-2007-4-1-IOF from the European Union [P.V.], the Swedish Brain Foundation and Swedish Society for Medicine [P.V.], the Institutes of Health: K24 AG035007 [R.S.], R01 AG027435-S1 [R.S.], P01AG036694 [R.S.], P50AG00513421 [R.S.], and the Alzheimer's Association: IIRG-06-27374 [R.S] and the Netherlands Organization
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