The structure of hippocampal circuitry relates to rapid category learning in humans

Abstract

Prior work suggests that complementary white matter pathways within the hippocampus (HPC) differentially support the learning of specific versus general information. In particular, while the trisynaptic pathway (TSP) rapidly forms memories for specific experiences, the monosynaptic pathway (MSP) slowly learns generalities.However, despite the theorized significance of such circuitry, characterizing how information flows within the HPC to support learning in humans remains a challenge.We leveraged diffusion-weighted imaging as a proxy for individual differences in white matter structure linking key regions along with TSP (HPC subfields CA 3 and CA 1 ) and MSP (entorhinal cortex and CA 1 ) and related these differences in hippocampal structure to category learning ability. We hypothesized that learning to categorize the "exception" items that deviated from category rules would benefit from TSPsupported mnemonic specificity. Participant-level estimates of TSP-and MSP-related integrity were constructed from HPC subfield connectomes of white matter streamline density. Consistent with theories of TSP-supported learning mechanisms, we found a specific association between the integrity of CA 3 -CA 1 white matter connections and exception learning. These results highlight the significant role of HPC circuitry in complex human learning.

A neural network model of hippocampal contributions to category learning

“…Indeed, several studies have found that activation in the anterior hippocampus is related to category learning (Mack et al, 2016(Mack et al, , 2018Zeithamova et al, 2008) and to prototypestyle learning specifically (Bowman & Zeithamova, 2018). Further, activation in the hippocampal body and tail is associated with learning categories that involve exceptions (Davis, Love, & Preston, 2012), which is also consistent with the finding that TSP white matter integrity predicts exception learning (Schlichting et al, 2021). Thus, neuroimaging evidence suggests a strong involvement of the hippocampus in category learning, with some evidence consistent with our account of the nature of this involvement.…”

“…Lesioning the TSP resulted in poor recognition with preserved categorization ability. Consistent with these behaviors, a recent study found that strong TSP white matter integrity predicts the ability to learn category exceptions (Schlichting, Gumus, Zhu, & Mack, 2021). We thus propose that the properties of the TSP should make it useful beyond its traditional domain of episodic memoryit should contribute to any new learning that requires memory for arbitrary, as opposed to systematic, information.…”

“…There are several empirical datapoints that already fit these predictions, including category-related similarity structure in CA1 (Schapiro et al, 2016), TSP white matter integrity predicting exception learning (Schlichting et al, 2021), and behavioral exception learning that unfolds in accordance with MSP and TSP properties (Heffernan, Schlichting, & Mack, 2021). But more work is needed to establish the extent to which, and the conditions under which, this account correctly characterizes the contribution of the hippocampus to category learning.…”

“…In rodent models, it is possible to separately lesion the two pathways (Nakashiba et al, 2008). There is also variance across people (or animals) in the normal anatomical integrity of the two pathways that can be measured (Schlichting et al, 2021). In general, we expect double dissociations in the behavior resulting from strength vs. weakness of the TSP vs. MSP: Weakness specifically in the TSP should result in poor memory for specific, arbitrary features of exemplars but preserved memory for structure shared across exemplars.…”

Clinical Neurophysiology of Epileptogenic Networks

“…The trisynaptic circuit of the hippocampus is organized transversely along the hippocampus. Association and commissural fibers are organized along the anteroposterior axis [63].…”