Biology subjects

Moscovitch, M.

Publications and source records attributed to Moscovitch, M..

10 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↗

bioRxiv2023

Organization of pRF size along the AP axis of the hippocampus is related to specialization for scenes

The hippocampus is largely recognized for its integral contributions to memory processing. By contrast, its role in perceptual processing remains less clear. Hippocampal properties differ along the anterior-posterior (AP) axis. Based on past research suggesting a gradient in the scale of features processed along the anterior-posterior extent of the hippocampus, the representations have been proposed to differ as a function of granularity along this axis. One way to quantify such granularity is with population receptive field (pRF) size measured during visual processing, which has so far received little attention. In this study, we compare the pRF sizes within the hippocampus to its activation for images of scenes versus faces. We also measure these functional properties in surrounding medial temporal lobe (MTL) structures. Consistent with past research, we find pRFs to be larger in anterior than in the posterior hippocampus. Critically, our analysis of surrounding MTL regions, such as the perirhinal cortex, entorhinal cortex and parahippocampal cortex, shows a similar relationship between scene sensitivity and larger pRF size. These findings provide conclusive evidence for a tight relationship between pRF size and the sensitivity to image content in the hippocampus.

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↗

bioRxiv2020

Pattern Separation Contributes to Categorical Face Perception

Traditionally considered a memory structure, the hippocampus has been shown to contribute to non-memory functions, from perception to language. Recent evidence suggests that the ability to differentiate highly confusable faces could involve pattern separation, a mnemonic process mediated by the hippocampal dentate gyrus (DG). Hippocampal involvement, however, may depend on existing face memories. To investigate these possibilities, we tested BL, a rare individual with bilateral lesions selective to the DG, and healthy controls. Both were administered morphed images of famous and nonfamous faces in a categorical perception (CP) identification and discrimination experiment. All participants exhibited nonlinear identification of famous faces with a midpoint category boundary. Controls identified newly learned nonfamous faces with lesser fidelity, while BL showed a notable shift in category boundary. When discriminating face pairs, controls showed typical CP effects of better between-category than within-category discrimination -- but only for famous faces. BL showed extreme within-category "compression," reflecting his tendency to pattern complete following suboptimal pattern separation. We provide the first evidence that pattern separation contributes to CP of faces.

neuroscience↗

bioRxiv2019

Recollection and prior knowledge recruit the left angular gyrus during recognition

The human angular gyrus (AG) is implicated in recollection, or our ability to retrieve detailed memory content from a specific study episode. Parallel work also highlights a key role of the AG in the representation of general knowledge and semantics. How these two lines of research converge remains unclear. The present fMRI experiment used a remember-know paradigm with famous and non-famous faces to test whether activity in the AG could be modulated by both task-specific recollection and general prior knowledge in the same participants. Increased BOLD activity in the left AG was observed during both recollection in the absence of prior knowledge (i.e., recollected > non-recollected or correctly rejected non-famous faces) and when prior knowledge was accessed in the absence of recollection (i.e., famous > non-famous correct rejections). This pattern was unique to the left AG, and was not present in any other regions of the lateral inferior parietal lobe. Furthermore, the response profile of the left AG was consistent with accounts of recollection strength. Recollection-related activity was greater for faces with longer exposures at encoding than those with shorter exposures and was greater for stimuli with prior knowledge than those without, despite prior knowledge being incidental to the recognition decision. Therefore, the left AG is recruited during the access of both task-specific recollection and general prior knowledge, with greater activity as the amount of retrieved information increases, irrespective of its episodic or semantic nature. Significance StatementThe human angular gyrus (AG) is often implicated in our ability to remember past events. A separate line of research examining our ability to represent general knowledge has also highlighted the AG as a core region of interest. To reconcile these separate views of AG function, we used fMRI to test whether the human left AG was sensitive to remembering details from a specific study episode (i.e., recollection) or more general prior knowledge, within the same participants. Overall, activity in the left AG was sensitive to both recollection and prior knowledge, suggesting any complete functional account of the left AG during retrieval must consider its sensitivity to both kinds of mnemonic representations.

neuroscience↗

bioRxiv2018

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

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bioRxiv2017

Spontaneous Pre-encoding Activation of Neural Patterns Predicts Memory ‎

It is well-established that whether information will be remembered or not depends on the extent to which the learning context is reinstated during post-encoding rest and/or at retrieval. It has yet to be determined, however, if the fundamental importance of reinstatement to memory extends to periods of spontaneous neurocognitive activity prior to learning. We thus asked whether memory performance can be predicted by the extent to which spontaneous pre-encoding neural patterns resemble patterns elicited during encoding. Individuals studied and retrieved lists of words while undergoing fMRI-scanning. Multivoxel hippocampal patterns during resting periods prior to encoding resembled hippocampal patterns at encoding most strongly for items that were subsequently remembered. Furthermore, across subjects, the magnitude of similarity correlated with a behavioural measure of episodic recall. The results indicate that the neural scaffold of a memory trace is spontaneously laid even before ever perceiving the to-be-encoded information.\n\nSignificance StatementIt is well-established that memory performance depends on the degree to which the learning-context is reinstated during post-learning rest or during retrieval. However, does memory also depend on the context prior to learning--namely, on processes occurring spontaneously before ever perceiving the to-be-learned information? To answer this question, we scanned participants using fMRI while they were learning and recalling word-lists and, crucially, also during resting periods before each list. Patterns of brain activity in memory-related regions which were elicited spontaneously during these resting periods resembled patterns during learning. Furthermore, the greater this resemblance, the better was memory performance. We demonstrate that memory can be predicted by the degree to which patterns of neural activity prior to learning are reinstated during learning.

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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.

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bioRxiv2017

Long-term consolidation switches goal proximity coding from hippocampus to retrosplenial cortex

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (> 2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the proximity to the goal in the newly learned campus, but not in the familiar campus. By contrast retrosplenial cortex tracked the distance to the goal in the familiar campus, but not in the recently learned campus. These responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and help advance models of how neural circuits support navigation in novel and highly familiar environments.\n\nSignificance StatementHistorically, research on the hippocampal formation has focused on its role in long-term memory and navigation - often in isolation. No study to date has directly compared realistic navigation within familiar with recently learned environments, nor has it been explored how the neural substrates, along with computational codes, may change. In this study, we show for the first time, a shift from hippocampal to cortical coding of distance to a goal during active navigation. This study bridges the gap between memory consolidation and navigation, and paves the way for more functional and realistic understanding of the hippocampus.

neuroscience↗