Dentate Gyrus Integrity Is Necessary for Behavioral Pattern Separation But Not Statistical Learning

Abstract

Pattern separation, the creation of distinct representations of similar inputs, and statistical learning, the rapid extraction of regularities across multiple inputs, have both been linked to hippocampal processing. It has been proposed that there may be functional differentiation within the hippocampus, such that the trisynaptic pathway (entorhinal cortex > dentate gyrus > CA3 > CA1) supports pattern separation, whereas the monosynaptic pathway (entorhinal cortex > CA1) supports statistical learning. To test this hypothesis, we investigated the behavioral expression of these two processes in B. L., an individual with highly selective bilateral lesions in the dentate gyrus that presumably disrupts the trisynaptic pathway. We tested pattern separation with two novel auditory versions of the continuous mnemonic similarity task, requiring the discrimination of similar environmental sounds and trisyllabic words. For statistical learning, participants were exposed to a continuous speech stream made up of repeating trisyllabic words. They were then tested implicitly through a RT-based task and explicitly through a rating task and a forced-choice recognition task. B. L. showed significant deficits in pattern separation on the mnemonic similarity tasks and on the explicit rating measure of statistical learning. In contrast, B. L. showed intact statistical learning on the implicit measure and the familiarity-based forced-choice recognition measure. Together, these results suggest that dentate gyrus integrity is critical for high-precision discrimination of similar inputs, but not the implicit expression of statistical regularities in behavior. Our findings offer unique new support for the view that pattern separation and statistical learning rely on distinct neural mechanisms.

A neural network model of hippocampal contributions to category learning

“…Our proposal is that the MSP is responsible for that hippocampal contribution. This predicts that patients with specific TSP damage should be unimpaired in category learning, consistent with recent evidence of preserved statistical learning performance in a patient with specific DG damage ( Wang et al, 2023 ).…”

Differential effects of bilateral hippocampal CA3 damage on the implicit learning and recognition of complex event sequences

“…Evidence of preserved sequence learning following CA3 damage would suggest that the monosynaptic pathway is sufficient to support the learning of deterministic regularities. In line with the model by Schapiro et al ( 2017 ), a recent case study, based on an individual with selective bilateral damage to the DG, demonstrated that performance was intact on a statistical learning task, which required the rapid generalization and extraction of commonalities shared across multiple auditory events, despite a deficit in the ability to pattern separate (i.e., transform overlapping representations into distinct ones) (Wang et al, 2023 ).…”

“…Importantly, the hippocampus is not an unitary anatomical structure, rather it is comprised of subregions with differing firing properties, connectivity, and function (Baker et al, 2016 ; Bartsch et al, 2011 ; Dalton et al, 2022 ; Kesner & Rolls, 2015 ; Miller et al, 2017 , 2020 ). However, lesion studies of implicit sequence learning in humans have averaged across subregions (Curran, 1997 ; Reber & Squire, 1998 ; Shanks et al, 2006 ), largely because hippocampal damage seldom affects a single subfield or remains confined to the hippocampus (Baker et al, 2016 ; Bartsch et al, 2011 ; Miller et al, 2017 , 2020 ; Wang et al, 2023 ).…”

Heterogenous effect of early adulthood stress on cognitive aging and synaptic function in the dentate gyrus

“…Chronic mild stress exposure led to a decrease in the expression of synaptophysin in the dentate gyrus, indicating a detrimental effect on the integrity of the synapses ( Wang et al, 2012 ). These morphological changes are associated not only with aging ( Geinisman et al, 1992 ; Hara et al, 2012 ) but also with the enduring impact of remote life-long stress ( Herrmann et al, 2012 ), and may be related to imprecise memory discrimination ( Chenani et al, 2022 ; Wang et al, 2023 ).…”