Integrating new findings and examining clinical applications of pattern separation

Abstract

Pattern separation, the ability to independently represent and store similar experiences, is a crucial facet of episodic memory. Growing evidence suggests that the hippocampus possesses unique circuitry that is computationally capable of resolving mnemonic interference by using pattern separation. In this Review, we discuss recent advances in the understanding of this process and evaluate the caveats and limitations of linking across animal and human studies. We summarize clinical and translational studies using methods that are sensitive to pattern separation impairments, an approach that stems from the fact that the hippocampus is a major site of disruption in many brain disorders. We critically evaluate the assumptions that guide fundamental and translational studies in this area. Finally, we suggest guidelines for future research and offer ways to overcome potential interpretational challenges to increase the utility of pattern separation as a construct that can further understanding of both memory processes and brain disease.

ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

“…Another core DMN node, the medial temporal lobe (MTL) is one of the earliest brain regions where tau tangles aggregate, and its sub‐regions show a selective topography of pathological involvement during early AD (Braak & Braak, ). The formation of tau neurofibrillary tangles is first seen in the transentorhinal and entorhinal cortex (EC) (Braak & Braak, , ) followed by the dentate gyrus (DG) and CA3 subfield in the hippocampus (Leal & Yassa, ). Although their pathological relationship remains unclear (Mann & Hardy, ), MTL tau is considerably increased in normal subjects with cortical Aβ (Braak, Thal, Ghebremedhin, & Del Tredici, ; Sperling, Mormino, & Johnson, ).…”

“…Another core DMN node, the medial temporal lobe (MTL) is one of the earliest brain regions where tau tangles aggregate, and its subregions show a selective topography of pathological involvement during early AD (Braak & Braak, 1991). The formation of tau neurofibrillary tangles is first seen in the transentorhinal and entorhinal cortex (EC) (Braak & Braak, 1991, 1997 followed by the dentate gyrus (DG) and CA3 subfield in the hippocampus (Leal & Yassa, 2018).…”

Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults

“…For example, older rats have been found to have, among other decrements, worse recollection (Robitsek, Fortin, Koh, Gallagher, & Eichenbaum, 2008), spatial memory (Barnes, 1979), and pattern separation (Burke et al, 2011) than young rats. Similarly, in humans, age is related to worse performance on relational memory tasks that target binding processes (Naveh-Benjamin, 2000;Naveh-Benjamin, Hussain, Guez, & Bar-On, 2003), and mnemonic discrimination tasks that target pattern separation processes (for review see Leal & Yassa, 2018;Reagh et al, 2016).…”

Regulation of gamma‐frequency oscillation by feedforward inhibition: A computational modeling study

“…Our results indicate that feedforward inhibition enhances the level of selection, enforcing sparseness (note that augmenting the level of selection leads to fewer cells firing, which, in turn, manifests itself as an increasing level of sparseness). Therefore, a possible effect of the impairment of the feedback inhibition would be observed in tasks in which sparseness of activity is important, such as pattern separation (Leal & Yassa, ) or memory storage (de Almeida et al, ). Such effects would be most likely to take place in brain structures known to have sparse activity such as the hippocampus (Wixted et al, ), especially the dentate gyrus (Berron et al, ; de Almeida et al, ; Leutgeb et al, ; Leutgeb & Leutgeb, ; Rennó‐Costa et al, ).…”