Longitudinal relations between sleep quality, psychological distress, and cognitive function among rural older adults: a cross-lagged network analysis.

Hippocampal pattern separation is a neural operation responsible for creating orthogonalized representations from overlapping inputs (–). Converging evidence from animal (–), human (–), as well as clinical (–) studies suggest that the dentate gyrus (DG) subfield of the hippocampus is critical in establishing this sparsification (–). The resulting sparse signal is then forwarded via mossy fibers to the cornu ammonis 3 (CA3) () where separated representations are also observable (, ). At the cognitive level, in humans, pattern separation supports mnemonic discrimination (–)—sometimes referred to as “behavioral pattern separation” (, )—i.e., successfully detecting novelty of lures that are highly similar to already encoded memory traces. This is often assessed via the mnemonic similarity task (MST) (, ), which tests mnemonic discrimination of highly similar pictures of everyday objects. At the neural level, the most typical operationalization of pattern separation in humans leverages the alteration of region-specific blood oxygen related (BOLD) signal upon repetition of a stimulus [i.e., repetition suppression (RS) effect] (, , ). This “repetition sensitivity approach” () allows identification of regions [within and beyond the HC ()] that treat a stimulus as a repetition of a previously presented stimulus. Importantly, it further allows to distinguish clusters within these repetition sensitive regions that respond to similar lures as repetitions from those that respond to similar lures as novel stimuli. A core assumption of this approach is that the regions treating similar lures as novel perform pattern separation. Parametrically manipulating the degree of similarity between lures and encoded traces allows for a fine-grained measurement of such differences in RS (). Based on converging evidence from human fMRI studies, regions that perform pattern separation, should exhibit 1) attenuated RS to similar lures, suggesting that these are treated as novel rather than repeated items (–, ), 2) an activation pattern with small differences in input leading to large differences in output with moderate or no further effect of increased input differences (, , –), and 3) sensitivity to mnemonic discrimination success, such that falsely recognized lures elicit decreased activity compared to correctly rejected ones (, –).