Biology subjects

Schlichting, M. L.

Publications and source records attributed to Schlichting, M. L..

6 recordsLinked to original sources

bioRxiv2026

Children and adults use distinct neurocognitive mechanisms to support successful memory-based inference

Reasoning depends on the ability to connect information across distinct experiences to derive knowledge that was never directly observed, and this capacity exhibits protracted developmental improvement that extends into emerging adulthood. Despite extensive behavioral work, it remains unclear whether developmental gains in inference reflect quantitative strengthening of a single mechanism or qualitative changes in the knowledge representations and computations that support inference decisions. Here, we tested the hypothesis that improvements in inference are linked to maturation of the hippocampus and posterior parietal cortex, resulting in age-related differences in how inference decisions are computed. We predicted that children (7-12 years) would rely on an iterative retrieval mechanism, requiring retrieval and combination of multiple distinct memories at the time of inference, whereas adults would be able to directly retrieve inferred relationships from structured representations that encode shared relations across experiences. Using functional MRI combined with computational modeling of response times, we show that hippocampal activity predicts successful inference via an iterative retrieval mechanism in both children and adults. Critically, only in adults does angular gyrus activity predict inference via a distinct, direct retrieval mechanism, consistent with access to inferred relationships represented as either integrated memories or in geometrically aligned neural spaces that organize events according to their shared relational structure. These findings identify a developmental shift in the neural mechanisms that support inference, demonstrating that maturation of posterior parietal cortex enables access to representations that capture derived linkages across experiences, fundamentally changing how inference decisions are computed across development.

neuroscience↗

bioRxiv2025

Development of anterior hippocampal integration underlies the protracted emergence of cognitive map formation and generalization

Flexible memory depends on cognitive maps that integrate spatial relationships and guide behavior as environments change. The anterior hippocampus is well positioned to support integration across broad spatiotemporal scales, but its late maturation may constrain development of flexible, map-based navigation. Here, we tested whether hippocampal temporal autocorrelation, an index of neural activity stability over time, tracks the development of spatial integration. In a large resting-state fMRI sample (N = 382; ages 5-34 years), temporal autocorrelation increased with age in anterior, but not posterior, hippocampus. This anterior-specific pattern was replicated in an independent task-based fMRI sample of children, adolescents, and adults (N = 85; aged 6-12 years and adults), wherein we linked hippocampal autocorrelation to dissociable components of spatial behavior. The navigation task separated memory for object locations from the ability to update and generalize knowledge across rotations of the distal reference frame and to new object sets. Although all age groups learned object locations, only older participants showed evidence that prior spatial structure supported performance as the environment changed across runs. Critically, hippocampal autocorrelation related to behavior only when spatial knowledge was used across runs, rather than improved through within-run feedback, with the clearest profile emerging in adults. In adults, anterior and posterior autocorrelation jointly predicted precise object-location memory, whereas anterior autocorrelation uniquely predicted efficient trajectories from novel starting positions. These findings identify anterior hippocampal temporal autocorrelation as a later-maturing computation that supports the transition from local spatial learning in childhood to flexible navigation through changing environments in adulthood. Significance StatementFinding our way through the world requires more than remembering where things are. We also need to use what we have learned to take new routes, adjust when familiar places change, and apply old knowledge to new situations. These abilities improve from childhood to adulthood, but the brain changes that support this transition remain unclear. We show that a signal in anterior hippocampus, a brain region important for linking experiences, becomes more stable over development. Using a navigation task that separated remembering object locations from flexibly using a map, we found that this signal was most strongly tied to adults ability to navigate efficiently through changing environments. These findings reveal a hippocampal mechanism that supports flexible navigation as children mature.

neuroscience↗

bioRxiv2025

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically-valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI (http://www.hippocampalsubfields.com). Here, we report the first portion of the protocol focused on subfields in the hippocampal body; protocols for the head and tail are in development. The body protocol includes definitions of the internal boundaries between subiculum, Cornu Ammonis (CA) 1-3 subfields, and dentate gyrus, in addition to the external boundaries of the hippocampus apart from surrounding white matter and cerebrospinal fluid. The segmentation protocol is based on a novel histological reference data set labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. All boundary definitions were rated as having high clarity and reached consensus agreement by Delphi procedure. The harmonized body protocol yielded high inter- and intra-rater reliability. In the present paper we report the procedures to develop and test the protocol, as well as the detailed procedures for manual segmentation using the harmonized protocol. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in neurodegenerative diseases.

neuroscience↗

bioRxiv2023

Differentiation of related events in hippocampus supports memory reinstatement in development

Adults are capable of either differentiating or integrating similar events in memory based on which representations are optimal for a given situation. Yet how children represent related memories remains unknown. Here, children (7-10 years) and adults formed memories for separate yet overlapping events. We then measured how successfully remembered events were represented and reinstated using functional magnetic resonance imaging (fMRI). We found that children formed differentiated representations in hippocampus--such that related events were stored as less similar to one another compared to unrelated events. Conversely, adults formed integrated representations, wherein related events were stored as more similar, including in medial prefrontal cortex (mPFC). Furthermore, hippocampal differentiation among children and mPFC integration among adults tracked neocortical reinstatement of the specific features associated with the individual events. Together, these findings reveal that the same memory behaviors are supported by different underlying representations across development. Specifically, whereas differentiation underlies memory organization and retrieval in childhood, integration exhibits a protracted developmental trajectory.

neuroscience↗

bioRxiv2021

The structure of hippocampal trisynaptic pathway relates to rapid category learning in humans

Prior work suggests that complementary white matter pathways within the hippocampus differentially support 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 hippocampus (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 TSP (HPC subfields CA3 and CA1) and MSP (entorhinal cortex and CA1) 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 TSP-supported 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 CA3-CA1 white matter connections and exception learning. These results highlight the significant role of HPC circuitry in complex human learning.

neuroscience↗

bioRxiv2018

Predictability changes what we remember in familiar temporal contexts

The human brain constantly anticipates the future based on memories of the past. Encountering a familiar situation reactivates memory of previous encounters which can trigger a prediction of what comes next to facilitate responsiveness. However, a prediction error can lead to pruning of the offending memory, a process that weakens its representation in the brain and leads to forgetting. Our goal in this study was to evaluate whether memories are spared from pruning in situations that allow for more abstract yet reliable predictions. We hypothesized that when the category, but not the identity, of a new stimulus can be anticipated, this will reduce pruning of existing memories and also reduce encoding of the specifics of new memories. Participants viewed a sequence of objects, some of which reappeared multiple times ("cues"), followed always by novel items. Half of the cues were followed by new items from different (unpredictable) categories, while others were followed by new items from a single (predictable) category. Pattern classification of fMRI data was used to identify category-specific predictions after each cue. Pruning was observed only in unpredictable contexts, while encoding of new items suffered more in predictable contexts. These findings demonstrate that how episodic memories are updated is influenced by the reliability of abstract-level predictions in familiar contexts.

neuroscience↗