Biology subjects

Barense, M. D.

Publications and source records attributed to Barense, M. D..

11 recordsLinked to original sources

bioRxiv2025

Discrete Subfields and Continuous Gradients Coexist: A Multi-Scale View of Hippocampal Organization

The human hippocampus is studied via two competing frameworks: one dividing it into discrete anatomical subfields with distinct computational processes, and another describing it as a continuous, functional gradients along the anterior-posterior and medial-lateral axes. How these organizational principles relate to one another, particularly regarding intrinsic neural timescales of the hippocampus, remains unknown. Here, we used high-resolution resting-state fMRI to investigate how single-voxel autocorrelation, a measure of intrinsic neural timescale, maps onto hippocampal subfields. We found evidence for a hybrid organization. First, consistent with our predictions, we observed significantly higher autocorrelation (longer timescales) in the subiculum compared to the other subfields. Contrary to our hypotheses, we found that CA1, which is implicated in integration, had low autocorrelation whereas CA2/3 and CA4DG, which are linked to pattern separation, had intermediate autocorrelation. Second, we discovered that the overarching anterior-posterior and medial-lateral gradients of autocorrelation were recapitulated within each individual subfield. Finally, data-driven clusters of autocorrelation values aligned more strongly with the continuous gradients than with the discrete anatomical boundaries, particularly in the right hemisphere. These results suggest that the discrete and continuous views of hippocampal organization are not mutually exclusive but coexist across different spatial scales. We therefore propose a new comprehensive model of hippocampal function that integrates both its modular, subfield-specific properties and its graded, large-scale organization.

neuroscience↗

bioRxiv2023

Single voxel autocorrelation reflects hippocampal function in temporal lobe epilepsy

We have previously shown that autocorrelation analyses of BOLD signal applied to single voxels in healthy controls can identify behaviorally-relevant gradients of temporal dynamics throughout the hippocampal long-axis. A question that remains is how changes in the brains functional and structural integrity affect single voxel autocorrelation. In this study we investigate how hippocampal autocorrelation is affected by hippocampal dysfunction by investigating a population of patients with unilateral temporal lobe epilepsy (TLE). Many patients with TLE have mesial temporal sclerosis (MTS), characterized by scarring and neuronal loss particularly in the anterior hippocampus. Here we compared patients with left and right TLE, some with and without MTS, to healthy controls. We applied our single voxel autocorrelation method and data-driven clustering approach to segment the hippocampus based on the autocorrelation of resting state fMRI. We found that patients with left TLE had longer intrinsic timescales (i.e., higher autocorrelation) compared to controls, particularly in the anterior-medial portion of the hippocampus. This was true for both the epileptogenic and non-epileptogenic hemispheres. We also evaluated the extent of cluster preservation (i.e., spatial overlap with controls) of patient autocorrelation clusters and the relationship to verbal and visuospatial memory. We found that patients with greater cluster preservation in the anterior-medial hippocampus had better memory performance. Surprisingly, we did not find any effect of MTS on single voxel autocorrelation, despite the structural changes associated with the condition. These results suggest that spatiotemporal dynamics of activity can be informative regarding the functional integrity of the hippocampus in TLE.

neuroscience↗

bioRxiv2022

Multimodal Object Representations Rely on Integrative Coding

Combining information from multiple senses is essential to object recognition. Yet how the mind combines sensory input into coherent multimodal representations - the multimodal binding problem - remains poorly understood. Here, we applied multi-echo fMRI across a four-day paradigm, in which participants learned 3-dimensional multimodal object representations created from well-characterized visual shape and sound features. Our novel paradigm decoupled the learned multimodal object representations from their baseline unimodal shape and sound features, thus tracking the emergence of multimodal concepts as they were learned by healthy adults. Critically, the representation for the whole object was different from the combined representation of its individual parts, with evidence of an integrative object code in anterior temporal lobe structures. Intriguingly, the perirhinal cortex - an anterior temporal lobe structure - was by default biased towards visual shape, but this initial shape bias was attenuated with learning. Pattern similarity analyses suggest that after learning the perirhinal cortex orthogonalized combinations of visual shape and sound features, transforming overlapping feature input into distinct multimodal object representations. These results provide evidence of integrative coding in the anterior temporal lobes that is distinct from the distributed sensory features, advancing the age-old question of how the mind constructs multimodal objects from their component features.

neuroscience↗

bioRxiv2021

Single voxel autocorrelation uncovers gradients of temporal dynamics in the hippocampus and entorhinal cortex during rest and navigation

During navigation, information at multiple scales needs to be integrated. Single- unit recordings in rodents suggest that gradients of temporal dynamics in the hippocampus and entorhinal cortex support this integration. In humans, gradients of representation are observed, such that granularity of information represented increases along the long axis of the hippocampus. The neural underpinnings of this gradient in humans, however, are still unknown. Current research is limited by coarse fMRI analysis techniques that obscure the activity of individual voxels, preventing investigation of how moment-to-moment changes in brain signal are organized and how they are related to behavior. Here, we measured the signal stability of single voxels over time to uncover previously unappreciated gradients of temporal dynamics in the hippocampus and entorhinal cortex. Using our novel, single voxel autocorrelation technique, we show a medial-lateral hippocampal gradient, as well as a continuous autocorrelation gradient along the anterolateral- posteromedial entorhinal extent. Importantly, we show that autocorrelation in the anterior-medial hippocampus was modulated by navigational difficulty, providing the first evidence that changes in signal stability in single voxels are relevant for behavior. This work opens the door for future research on how temporal gradients within these structures support the integration of information for goal- directed behavior.

neuroscience↗

bioRxiv2021

The Similarity Structure of Real-World Memories

How do we mentally organize our memories of life events? Two episodes may be connected because they share a similar location, time period, activity, spatial environment, or social and emotional content. However, we lack an understanding of how each of these dimensions contributes to the perceived similarity of two life memories. We addressed this question with a data-driven approach, eliciting pairs of real-life memories from participants. Participants annotated the social, purposive, spatial, temporal, and emotional characteristics of their memories. We found that the overall similarity of memories was influenced by all of these factors, but to very different extents. Emotional features were the most consistent single predictor of overall memory similarity. Memories with different emotional tone were reliably perceived to be dissimilar, even when they occurred at similar times and places and involved similar people; conversely, memories with a shared emotional tone were perceived as similar even when they occurred at different times and places, and involved different people. A predictive model explained over half of the variance in memory similarity, using only information about (i) the emotional properties of events and (ii) the primary action or purpose of events. Emotional features may make an outsized contribution to event similarity because they provide compact summaries of an events goals and self-related outcomes, which are critical information for future planning and decision making. Thus, in order to understand and improve real-world memory function, we must account for the strong influence of emotional and purposive information on memory organization and memory search. SignificanceOur brains enable us to understand and act within the present, informed by previous, related life experience. But how are our life experiences organized so that one event can be related to another? Theories have suggested that we use spatiotemporal, social, causal, purposive, and emotional dimensions to inter-relate our memories; however, these organizing principles are usually studied using impersonal laboratory stimuli. Here, we mapped and modeled the connections between peoples own annotated life memories. We found that life events are linked by a variety of factors, but are predominantly connected in memory by their primary activity and emotional character. This highlights a need for theories of memory organization and retrieval to better account for the role of high-level actions and emotions.

animal behavior and cognition↗

bioRxiv2020

Prediction errors during naturalistic events modulate hippocampal representations and drive episodic memory updating

The brain supports adaptive behavior by generating predictions, learning from errors, and updating memories to incorporate new information. Prediction error, or surprise, triggers learning when reality contradicts expectations. Prior studies have shown that the hippocampus signals prediction errors, but the hypothesized link to memory updating has not been demonstrated. In a human fMRI study, we elicited mnemonic prediction errors by interrupting familiar narrative videos immediately before the expected endings. We found that prediction error reversed the relationship between univariate hippocampal activation and memory: greater hippocampal activation predicted memory preservation after expected endings, but memory updating after surprising endings. In contrast to previous studies, we showed that univariate activation was insufficient for understanding hippocampal prediction error signals. We explained this surprising finding by tracking both the evolution of hippocampal activation patterns and connectivity between the hippocampus and neuromodulatory regions. We found that hippocampal activation patterns stabilized as each narrative episode unfolded, suggesting sustained episodic representations. Prediction errors disrupted these sustained representations, and the degree of disruption predicted memory updating. The relationship between hippocampal activation and subsequent memory depended on concurrent basal forebrain activation, supporting the idea that cholinergic modulation regulates attention and memory. We conclude that prediction errors create conditions that favor memory updating, prompting the hippocampus to abandon ongoing predictions and make memories malleable. SignificanceOur brains draw on memories to predict the future; when our predictions are incorrect, we must update our memories to improve future predictions. Past studies have demonstrated that the hippocampus signals prediction error, or surprise, but have not linked this neural signal to memory updating. Here, we uncover this missing connection: We show that mnemonic prediction errors change the role of the hippocampus, reversing the relationship between hippocampal activation and memory outcomes. We examine the mechanisms of this shift in neural processing, showing that prediction errors disrupt the temporal continuity of hippocampal patterns. We propose that prediction errors disrupt sustained representations and enable memory updating. Our findings bear implications for improving education, understanding eyewitness memory distortion, and treating pathological memories.

neuroscience↗

bioRxiv2019

Temporal integration of narrative information in a hippocampal amnesic patient

Default network regions appear to integrate information over time windows of 30 seconds or more during narrative listening. Does this long-timescale capability require the hippocampus? Amnesic behavior suggests that the hippocampus may not be needed for online processing when input is continuous and semantically rich: amnesics can participate in conversations and tell stories spanning minutes, and when tested immediately on recently heard prose their performance is relatively preserved. We hypothesized that default network regions can integrate the semantically coherent information of a narrative across long time windows, even in the absence of the hippocampus. To test this prediction, we measured BOLD activity in the brain of a hippocampal amnesic patient (D. A.) and healthy control participants while they listened to a seven-minute narrative. The narrative was played either in its intact form, or as a paragraph-scrambled version, which has been previously shown to interfere with the long-range temporal dependencies in default network activity. In the intact story condition, D. A.s moment-by-moment BOLD activity spatial patterns were similar to those of controls in low-level auditory cortex as well as in some high-level default network regions (including lateral and medial posterior parietal cortex). Moreover, as in controls, D. A.s response patterns in medial and lateral posterior parietal cortex were disrupted when paragraphs of the story were presented in a shuffled order, suggesting that activity in these areas did depend on information from 30 seconds or more in the past. Together, these results suggest that some default network cortical areas can integrate information across long timescales, even in the absence of the hippocampus.

neuroscience↗

bioRxiv2019

Visual interference can help and hinder memory: Measuring memory fidelity using a novel circular shape space

Although we can all agree that interference induces forgetting, there is surprisingly little consensus regarding what type of interference most likely disrupts memory. We previously proposed that the similarity of interference differentially impacts the representational detail of color memory. Here, we extend this work by applying the Validated Circular Shape Space (Li et al., 2020) for the first time to a continuous retrieval task, in which we quantified both the visual similarity of distracting information as well as the representational detail of shape memory. We found that the representational detail of memory was systematically and differentially altered by the similarity of distracting information. Dissimilar distractors disrupted both fine- and coarse-grained information about the target, akin to memory erasure. In contrast, similar distractors disrupted fine-grained target information but increased reliance on coarse-grained information about the target, akin to memory blurring. Notably, these effects were consistent across two mixture models that each implemented a different scaling metric (either angular distance or perceived target similarity), as well as a parameter-free analysis that did not fit the mixture model. These findings suggest that similar distractors will help memory in cases where coarse-grained information is sufficient to identify the target. In other cases where precise fine-grained information is needed to identify the target, similar distractors will impair memory. As these effects have now been observed across both stimulus domains of shape and color, and were robust across multiple scaling metrics and methods of analyses, we suggest that these results provide a general set of principles governing how the nature of interference impacts forgetting.

neuroscience↗

bioRxiv2018

Object-in-Place Memory Predicted by Anterolateral Entorhinal Cortex and Parahippocampal Cortex Volume in Older Adults

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimers disease (AD). Improving our understanding of this regions cognitive role may help identify better cognitive tests for early detection of AD. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object (Yeung et al., 2017). In the present study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eyetracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context (Wilson et al., 2013), and object-trace memory, the memory for the former location of objects (Tsao, Moser, & Moser, 2013). In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex (PHC) selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

neuroscience↗

bioRxiv2017

Integrative and distinctive coding of perceptual and conceptual object features in the ventral visual stream

A tremendous body of research in cognitive neuroscience is aimed at understanding how object concepts are represented in the human brain. However, it remains unknown whether and where the visual and abstract conceptual features that define an object concept are integrated. We addressed this issue by comparing the neural pattern similarities among object-evoked fMRI responses with behavior-based models that independently captured the visual and conceptual similarities among these stimuli. Our results revealed evidence for distinctive coding of visual features in lateral occipital cortex, and conceptual features in the temporal pole and parahippocampal cortex. By contrast, we found evidence for integrative coding of visual and conceptual object features in perirhinal cortex. The neuroanatomical specificity of this effect was highlighted by results from a searchlight analysis. Taken together, our findings suggest that perirhinal cortex uniquely supports the representation of fully-specified object concepts through the integration of their visual and conceptual features.

neuroscience↗

bioRxiv2017

Differential spatiotemporal representations along the hippocampal long axis in humans

Increased place field size and signal autocorrelation along the dorsoventral hippocampal axis in rodents are considered a fundamental aspect of hippocampal organization, yet such evidence is lacking in humans. Using fMRI, we report corresponding evidence of increasing neural similarity from posterior to anterior hippocampus (dorsoventral homologues) in humans. These findings help account for observed shifting in representational granularity, from global context (anterior) to local details (posterior), along the hippocampal axis.

neuroscience↗