Big-Loop Recurrence within the Hippocampal System Supports Integration of Information across Episodes

Abstract

Recent evidence challenges the widely held view that the hippocampus is specialized for episodic memory, by demonstrating that it also underpins the integration of information across experiences. Contemporary computational theories propose that these two contrasting functions can be accomplished by big-loop recurrence, whereby the output of the system is recirculated back into the hippocampus. We use ultra-high-resolution fMRI to provide support for this hypothesis, by showing that retrieved information is presented as a new input on the superficial entorhinal cortex-driven by functional connectivity between the deep and superficial entorhinal layers. Further, the magnitude of this laminar connectivity correlated with inferential performance, demonstrating its importance for behavior. Our findings offer a novel perspective on information processing within the hippocampus and support a unifying framework in which the hippocampus captures higher-order structure across experiences, by creating a dynamic memory space from separate episodic codes for individual experiences.

Event conjunction: How the hippocampus integrates episodic memories across event boundaries

“…This reactivation would arise during the trough of the theta cycle (where LTD occurs) to ensure the reactivated trace is not bound to incoming sensory information, nor confounded by any encoding‐related replay occurring during the same period (Colgin, ; Hasselmo et al, ; Schapiro et al, ). Detailed information about the original event is reinstated in the neocortex and then circled back to the hippocampus, where the theta‐gamma code is recreated (Koster et al, ). Elements of the ongoing event are then appended to the recreated theta‐gamma code in the same way in which new elements were added to the code during the unfolding of the original event.…”

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

“…However, studies supporting relationships between CRF, hippocampal structure, and memory in older adults have primarily used spatial working memory and spatial object recall and recognition tasks. Although these tasks target some aspects of hippocampal function (e.g., spatial memory), they also emphasize one‐trial learning, and while one role of the hippocampus is to acquire relations from single episodes at a time (Henke, Buck, Weber, & Wieser, ), the hippocampus is also involved in actively maintaining novel information over short time periods (Ranganath & D'Esposito, ; Watson, Voss, Warren, Tranel, & Cohen, ) and dynamically integrating information that connects episodes over time (Koster et al, ). One‐trial learning does not capture this accumulation of relations over repeated occurrences with overlapping content, which requires discriminating between similar memories (e.g., seeing Bill at two coffee shops) while also accessing and strengthening the relationships between these experiences (e.g., Bill) with repeated occurrences.…”

European Ultrahigh‐Field Imaging Network for Neurodegenerative Diseases (EUFIND)

“…Clinical research: High‐resolution structural imaging with 7T MRI is ideally placed to complement molecular measures of tau and amyloid pathology by providing unique information on disease staging, as suggested by the research framework for AD [1]. We have specifically identified the following topics for future clinical research: Disease modeling: Taking advantage of the superior spatial resolution of 7T MRI, longitudinal multiparametric high‐resolution imaging could better inform mathematical models of disease progression and offer a safe and quick tool for repeat use in treatment trials. Functional assessment: Functional 7T MRI can reach submillimeter resolution [2,3], thereby allowing to functionally probe and assess the integrity of small anatomical structures, such as entorhinal cortex subregions, hippocampus subfields, locus coeruleus, and basal ganglia circuits. Such information would facilitate understanding of disease effect on brain functions from the earliest stages of AD and PD and to probe target engagement in drug trials. Nonamyloid/non–tau‐pathology: High‐resolution angiography at 7T can aid the detection of disease comorbidities such as vascular pathology. Differential diagnosis: Iron mapping with 7T MRI could help improve the differential diagnosis of neurodegenerative diseases, for example, across parkinsonian disorders. End‐point markers for clinical trials: Increased sensitivity to quantify neurodegeneration could offer a validated readout for use in controlled designs.…”

“…Functional assessment: Functional 7T MRI can reach submillimeter resolution [2,3], thereby allowing to functionally probe and assess the integrity of small anatomical structures, such as entorhinal cortex subregions, hippocampus subfields, locus coeruleus, and basal ganglia circuits. Such information would facilitate understanding of disease effect on brain functions from the earliest stages of AD and PD and to probe target engagement in drug trials.…”

“…Disease modeling: Taking advantage of the superior spatial resolution of 7T MRI, longitudinal multiparametric high-resolution imaging could better inform mathematical models of disease progression and offer a safe and quick tool for repeat use in treatment trials. Functional assessment: Functional 7T MRI can reach submillimeter resolution [2,3], thereby allowing to functionally probe and assess the integrity of small anatomical structures, such as entorhinal cortex subregions, hippocampus subfields, locus coeruleus, and basal ganglia circuits. Such information would facilitate understanding of disease effect on brain functions from the earliest stages of AD and PD and to probe target engagement in drug trials.…”