Biology subjects

Davachi, L.

Publications and source records attributed to Davachi, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Reactivation during sleep segregates the neural representations of episodic memories

Sleep involves the reactivation of recently acquired memories, thereby shaping the neural representations supporting them. An essential feature of episodic memory (i.e., memory for events) is the link between specific elements (e.g., a cake) and the context in which they were embedded (e.g., a birthday party). We investigated how reactivation during sleep impacts item-context binding. Participants (N = 22) formed stories linking together objects in unique contexts. Using functional MRI, we measured the overlap between neural representations for contextually linked objects. During a 90-min nap, some object memories were reactivated by unobtrusively presenting object-specific sounds. Across multiple brain regions, reactivation reduced the overlap between representations of contextually linked memories, promoting object specificity. Furthermore, reactivation reduced the representational overlap between contexts, thereby promoting context specificity. Taken together, data suggest that reactivation during sleep decontextualizes memories. These results inform our understanding of how sleep contributes to interlinked memories embedded in naturalistic contexts and demonstrate that memory reactivation during sleep changes representations of memories within their distinctive contexts.

neuroscience↗

bioRxiv2025

Spontaneous reinstatement of episodic memories in the developing human brain

Starting early in development, the hippocampus can support the formation of episodic memories, and yet how the developing brain stabilizes these memories to support their long-term accessibility has not been established. This study (N = 49; mean age = 11.68 years) examined how encoded episodic memories are stabilized in development. Using fMRI and multivariate analyses, we tracked neural reinstatement of newly learned item-location-context associations in youth. During encoding, hippocampus and visual cortex activity predicted later memory success. Crucially, during post-encoding rest, spontaneous pattern reinstatement in the angular gyrus and the pregenual medial prefrontal cortex (mPFC) also predicted memory, with age-related changes in the mPFC and superior frontal gyrus. These findings suggest that episodic memory stabilization during childhood and adolescence is broadly supported by developmental change within regions associated with mature function, advancing our understanding of how different memory stages contribute to how we learn and remember across the lifespan.

neuroscience↗

bioRxiv2025

Characterizing representational shaping of individual motor and object representations after sequence learning

Learning temporal regularities between pairs of events has been shown to shape neural representations in the medial temporal lobe, but it remains unclear whether representational changes generalize across memory domains. Here we used fMRI and multivoxel pattern similarity analyses to examine representational shaping as a consequence of motor and object sequence learning. Across two sessions, participants incidentally learned a fixed four-element sequence of finger movements or visual objects. We compared the pattern of blood oxygen level-dependent activity evoked by each object and finger movement before and after sequence learning. Analyses were performed on bilateral ROIs, including primary motor cortex (M1), lateral occipital complex (LOC), premotor cortex (PMC), striatum (STR) and the hippocampus (HC). Behaviorally, participants successfully learned the sequence in both domains. At the neural level, motor representations became more differentiated with learning in M1, PMC, STR, and HC, but not in LOC. This global differentiation was not specific to the sequence condition and was also observed after repeated co-occurrence of movements in a pseudorandom order. Critically, the HC differentiated between motor representations in the learned sequence in a unidirectional predictive manner whereby movements became more differentiated from the preceding than from the following element in the sequence. In contrast, object representations remained stable across sequence repetitions in all brain regions, even though participants successfully learned their temporal order.

neuroscience↗

bioRxiv2025

Item recognition is associated with gut microbiota composition in healthy humans

Murine studies show that the gut microbiota - the collection of the microbes residing in the large intestine - affects memory performance in the host. However, whether commensal gut bacteria are linked to human episodic memory remains unknown. Here, we investigated whether individual differences in episodic memory performance were associated with differences in the indigenous gut microbiota composition between individuals. We show that greater gut microbiota alpha diversity was associated with better item recognition and that gut microbiota dissimilarity index (beta diversity) between participants was associated with differences in their performance. Finally, our results suggest that Prevotella copri might play a role in the relationship between gut microbiota and human item recognition in healthy individuals. In a sample size larger than previous human studies and examining unmanipulated gut microbiota, we provide evidence that episodic memory in healthy humans is linked to their gut microbiota composition. SIGNIFICANCE STATEMENTUnderstanding the relationship between the gut microbiota - the collective of microbes in our gut - and human cognition represents a pivotal frontier in neuroscience. Our study dives into this quest by exploring the connection between the indigenous gut microbiota and episodic memory in healthy individuals. While prior research has illuminated this relationship in murine models, our study extends these findings to humans, providing compelling evidence that gut microbiota diversity and structural composition are associated with differences in episodic memory performance. By shifting the focus from probiotic-based interventions to the study of our commensal gut microbes, our findings shed light on how the gut microbiota, in its natural state, could be linked to interindividual differences in human cognition.

animal behavior and cognition↗

bioRxiv2024

Locus coeruleus activation 'resets' hippocampal event representations and separates adjacent memories

Memories reflect the ebb and flow of experiences, capturing distinct events from our lives. Using a combination of functional magnetic resonance imaging (fMRI), neuromelanin imaging, and pupillometry, we show that arousal and locus coeruleus (LC) activation segment continuous experiences into discrete memories. As sequences unfold, encountering a context shift, or event boundary, triggers pupil-linked arousal and LC processes that predict later memory separation. Boundaries furthermore promote temporal pattern separation within left hippocampal dentate gyrus, which correlates with heightened LC responses to those same transition points. Unlike transient LC effects, indirect structural and functional markers of elevated background LC activation correlate with reduced arousal-related LC and pupil responses at boundaries, suggesting that hyperarousal disrupts event segmentation. Our findings support the idea that arousal mechanisms initiate a neural and memory reset in response to significant changes, fundamentally shaping the episodes that define episodic memory.

neuroscience↗

bioRxiv2023

Evidence for impaired hippocampal circuitry in schizophrenia and its link to memory dysfunction

Pattern separation and pattern completion are opposing yet complementary components of mnemonic processing that heavily rely on the hippocampus. It has been shown that processing within the dentate gyrus (DG) subfield promotes pattern separation while operations within the CA3 subfield are important for pattern completion. Schizophrenia has been associated with anatomical and functional hippocampal abnormalities, including within the DG and CA3. We hypothesized that an impairment in hippocampal circuitry in individuals with first-episode schizophrenia leads to deficits in pattern separation (mnemonic discrimination) and pattern completion (recognition memory), that these deficits contribute to delusions, and that antipsychotic treatment improves circuit functioning. We measured behavioral and neural responses during the identification of new, repeated, and similar stimuli using high-resolution fMRI in 45 medication-free or minimally-treated patients with first-episode schizophrenia and 49 matched controls. We found recognition memory and pattern separation deficits in patients and a negative association between memory performance and the severity of delusions. Neural analyses revealed deficits in both univariate BOLD responses and multivariate patterns in the hippocampus during mnemonic discrimination in patients compared to controls. Importantly, by investigating the association between trial-level neural activity and behavior before and after treatment, we found that antipsychotics normalized DG activity during pattern separation and CA3 activity during pattern completion. Lastly, trial-level cortical responses during mnemonic discrimination predicted performance in patients at baseline, suggesting a compensatory role. This study provides new insight into the impact of schizophrenia and antipsychotic treatment on memory systems and uncovers systems-level contributions to pattern separation and pattern completion.

neuroscience↗

bioRxiv2023

The reach of reactivation: Effects of consciously-triggered versus unconsciously-triggered reactivation of associative memory

Newly formed memories are not passively stored for future retrieval; rather, they are reactivated offline and thereby strengthened and transformed. However, reactivation is not a uniform process: it occurs throughout different states of consciousness, including conscious rehearsal during wakefulness and unconscious processing during both wakefulness and sleep. In this study, we explore the consequences of reactivation during conscious and unconscious awake states. Forty-one participants learned associations consisting of adjective-object-position triads. Objects were clustered into distinct semantic groups (e.g., multiple fruits, vehicles, musical instruments) which allowed us to examine the consequences of reactivation on semantically-related memories. After an extensive learning phase, some triads were reactivated consciously, through cued retrieval, or unconsciously, through subliminal priming. In both conditions, the adjective was used as the cue. Reactivation impacted memory for the most distal association (i.e., the spatial position of associated objects) in a consciousness-dependent and memory-strength-dependent manner. First, conscious reactivation of a triad resulted in a weakening of other semantically related memories, but only those that were initially more accurate (i.e., memories with lower pre-reactivation spatial errors). This is similar to what has been previously demonstrated in studies employing retrieval-induced forgetting designs. Unconscious reactivation, on the other hand, benefited memory selectively for weak cued items. Semantically linked associations were not impaired, but rather integrated with the reactivated memory. Taken together, our results demonstrate that conscious and unconscious reactivation of memories during wakefulness have qualitatively different consequences on memory for distal associations. Effects are memory-strength-dependent, as has been shown for reactivation during sleep. Results support a consciousness-dependent inhibition account, according to which unconscious reactivation involves less inhibitory dynamics than conscious reactivation, thus allowing more liberal spread of activation. Our findings set the stage for additional exploration into the role of consciousness in memory structuring.

neuroscience↗

bioRxiv2022

Repetition accelerates neural markers of memory consolidation

No sooner is an experience over than its neural memory representation begins to be strengthened and transformed through the process of memory replay. Using fMRI, we examined how memory strength manipulated through repetition during encoding modulates post-encoding replay in humans. Results revealed that repetition did not increase replay frequency in the hippocampus. However, replay in cortical regions and hippocampal-cortical coordinated replay were significantly enhanced for repeated events, suggesting that repetition accelerates the consolidation process. Interestingly, we found that replay frequency in both hippocampus and cortex modulated behavioral success on an immediate associative recognition test for the weakly encoded information, indicating a significant role for post-encoding replay in rescuing once-presented events. Together, our findings highlight the relationships of replay to stabilizing weak memories and accelerating cortical consolidation for strong memories.

neuroscience↗

bioRxiv2022

Consolidation-dependent behavioral integration of sequences related to mPFC neural overlap and hippocampal-cortical connectivity

Systems consolidation theories propose two mechanisms that enable the behavioral integration of related memories: coordinated reactivation between hippocampus and cortex, and the emergence of cortical traces that reflect overlap across memories. However, there is limited empirical evidence that links these mechanisms to the emergence of behavioral integration over time. In two experiments, participants implicitly encoded sequences of objects with overlapping structure. Assessment of behavioral integration showed that response times during a recognition task reflected behavioral priming between objects that never occurred together in time but belonged to overlapping sequences. This priming was consolidation-dependent and only emerged for sequences learned 24 hours prior to the test. Critically, behavioral integration was related to changes in neural pattern similarity in the medial prefrontal cortex and increases in post-learning rest connectivity between the posterior hippocampus and lateral occipital cortex. These findings suggest that memories with a shared predictive structure become behaviorally and neurally integrated through a consolidation-related restructuring of the learned sequences, providing insight into the relationship between different consolidation mechanisms that support behavioral integration.

neuroscience↗

bioRxiv2022

Event integration and temporal pattern separation: how hierarchical knowledge emerges in hippocampal subfields through learning

Everyday life is composed of events organized by changes in contexts, with each event containing an unfolding sequence of occurrences. A major challenge facing our memory systems is how to integrate sequential occurrences within events while also maintaining their details and avoiding over-integration across different contexts. Here we asked if and how distinct hippocampal subfields come to hierarchically, and in parallel, represent both event context and subevent occurrences with learning. Participants viewed sequential events defined as sequences of objects superimposed on shared color frames while undergoing high-resolution fMRI. Importantly, these events were repeated to induce learning. Event segmentation, as indexed by increased reaction times at event boundaries, was observed in all repetitions. Temporal memory decisions were quicker for items from the same event compared to across different events, indicating that events shaped memory behavior. With learning, hippocampal CA3 multivoxel activation patterns clustered to reflect the event context, with more clustering correlated with behavioral facilitation during event transitions. In contrast, in the dentate gyrus temporally proximal items that belonged to the same event became associated with more differentiated neural patterns. A computational model explained these results by dynamic inhibition in the dentate gyrus. Additional similarity measures support the notion that CA3 clustered representations reflect shared voxel populations, while dentate gyrus distinct item representations reflect different voxel populations. These findings suggest an interplay between temporal differentiation in dentate gyrus and attractor dynamics in CA3. They advance our understanding of how knowledge is structured through integration and separation across time and context. SignificanceA major challenge of our memory system is to integrate experiences occurring in the same context to generalize context-appropriate knowledge, while also maintaining distinct representations of these same occurrences to avoid confusion. Here, we uncover a novel mechanism for hierarchical learning in the human hippocampus that might help to resolve this tension. In the CA3 subregion of the hippocampus, the neural representations of items presented sequentially in the same context, but not in different contexts, became more overlapping with learning. In contrast, adjacent items, appearing close in time and in the same context, became increasingly more differentiated in the dentate gyrus. Thus, multiple representations in different hippocampal subregions encoded in parallel might enable simultaneous generalization and specificity in memory.

neuroscience↗

bioRxiv2022

Principled clustering of functional signals reveals gradients in processing both within the anterior hippocampus and across its long axis

A particularly elusive puzzle concerning the hippocampus is how the structural differences along its long, anteroposterior axis might beget meaningful functional differences, particularly in terms of the granularity of information processing. One measure posits to quantify this granularity by calculating the average statistical independence of the BOLD signal across neighboring voxels, or inter-voxel similarity (IVS), and has shown the anterior hippocampus to process coarser-grained information than that in the posterior hippocampus. This model of the hippocampus, however, conflicts with a number of task-oriented findings, many of which have varied in their fMRI acquisition parameters and hippocampal parcellation methods. In order to reconcile these findings, we measured IVS across two separate resting-state fMRI acquisitions and compared the results across many of the most widely used parcellation methods in a large young-adult sample (Acquisition 1, N = 253; Acquisition 2, N = 183). Finding conflicting results across acquisitions and parcellations, we reasoned that a principled, data-driven approach to hippocampal parcellation is necessary. To this end, we implemented a group masked independent components analysis (mICA) to identify functional subunits of the hippocampus, most notably separating the anterior hippocampus into separate anterior-medial, anterior-lateral, and posteroanterior-lateral components. Measuring IVS across these components revealed a decrease in IVS along the medial-lateral axis of the anterior hippocampus but an increase from anterior to posterior. We conclude that representational granularity may not change linearly or unidirectionally across the hippocampus, and that moving the study of the hippocampus towards reproducibility requires grounding it in a functionally informed approach. Significance StatementProcessing information along hierarchical scales of granularity is critical for many of the feats of cognition considered most human. Recently, the changes in structure, cortical connectivity, and apparent functional properties across parcels of the hippocampal long axis have been hypothesized to underlie this hierarchical gradient in information processing. We show here, however, that the choice of parcellation method itself drastically affects the perceived granularity across the hippocampus, and that a principled, functionally informed approach to parcellation reveals gradients both within the anterior hippocampus and in non-linear form across the long axis. These results point to the issue of parcellation as a critical one in the study of the hippocampus and reorient interpretation of existing results.

neuroscience↗

bioRxiv2021

Identifying Causal Subsequent Memory Effects

Over 40 years of accumulated research has detailed associations between neuroimaging signals measured during a memory encoding task and later memory performance, across a variety of brain regions, measurement tools, statistical approaches and behavioral tasks. But the interpretation of these Subsequent Memory Effects (SMEs) remains unclear: if the identified signals reflect cognitive and neural mechanisms of memory encoding then the underlying neural activity must be causally related to future memory. However, almost all previous SME analyses do not control for potential confounders of this causal interpretation, such as serial position and item effects. We collect a large fMRI dataset and use a novel experimental design and analysis approach that allows us to statistically adjust for all exogenous confounding variables. We find that, using standard approaches without adjustment, we replicate several univariate and multivariate subsequent memory effects and are able to predict memory performance across people. However, we are unable to identify any signal that reliably predicts subsequent memory after adjusting for confounding variables, bringing into doubt the causal status of these effects. We apply the same approach to subjects judgments of learning collected during an encoding period, and show that these behavioral measures of encoding quality do predict memory after adjustments, suggesting that it is possible to measure signals at the time of encoding that reflect causal mechanisms but that existing neuroimaging measures may not have the precision and specificity to do so.

neuroscience↗

bioRxiv2021

Reward enhances memory via age-varying online and offline neural mechanisms across development

Reward motivation enhances memory through interactions between mesolimbic, hippocampal, and cortical systems -- both during and after encoding. Developmental changes in these distributed neural circuits may lead to age-related differences in reward-motivated memory and the underlying neural mechanisms. Converging evidence from cross-species studies suggests that subcortical dopamine signaling is increased during adolescence, which may lead to stronger memory representations of rewarding, relative to mundane, events and changes in the contributions of underlying subcortical and cortical brain mechanisms across age. Here, we used fMRI to examine how reward motivation influences the "online" encoding and "offline" post-encoding brain mechanisms that support long-term associative memory from childhood to adulthood in human participants of both sexes. We found that reward motivation led to both age-invariant enhancements and nonlinear age-related differences in associative memory after 24 hours. Furthermore, reward-related memory benefits were linked to age-varying neural mechanisms. During encoding, interactions between the prefrontal cortex and ventral tegmental area (VTA) were associated with better high-reward memory to a greater degree with increasing age. Pre- to post-encoding changes in functional connectivity between the anterior hippocampus and VTA were also associated with better high-reward memory, but more so at younger ages. Our findings suggest that there may be developmental differences in the contributions of offline subcortical and online cortical brain mechanisms supporting reward-motivated memory. Significance StatementA substantial body of research has examined the neural mechanisms through which reward influences memory formation in adults. However, despite extensive evidence that both reward processing and associative memory undergo dynamic change across development, few studies have examined age-related changes in these processes. We found both age-invariant and nonlinear age-related differences in reward-motivated memory. Moreover, our findings point to developmental differences in the processes through which reward modulates the prioritization of information in long-term memory - with greater early reliance on offline subcortical consolidation mechanisms and increased contribution of systems-level online encoding circuitry with increasing age. These results highlight dynamic developmental changes in the cognitive and neural mechanisms through which motivationally salient information is prioritized in memory from childhood to adulthood.

neuroscience↗

bioRxiv2021

Mnemonic content and hippocampal patterns shape judgments of time

Our experience of time can feel dilated or compressed, rather than reflecting true "clock time." Although many contextual factors influence the subjective perception of time, it is unclear how memory accessibility plays a role in constructing our experience of and memory for time. Here, we used a combination of behavioral and fMRI measures to ask the question of how memory is incorporated into temporal duration judgments. Behaviorally, we found that event boundaries, which have been shown to disrupt ongoing memory integration processes, result in the temporal compression of duration judgments. Additionally, using a multivoxel pattern similarity analysis of fMRI data, we found that greater temporal pattern change in the left hippocampus within individual trials was associated with longer duration judgments. Together, these data suggest that mnemonic processes play a role in constructing representations of time. Statement of RelevanceOur everyday experiences convey a powerful truth: That our perception of time often diverges from the reality of time. When enjoying an active vacation with family, time moves quickly: hours go by in minutes. When sitting through an unnecessary meeting, time moves slowly: minutes go by in hours. What is the origin of these phenomenologically compelling illusions of time perception? Past research has examined how a range of specific factors, from emotions to blinking, contribute to the distortion of time. Here, in contrast, we evaluate how the content and accessibility of our memories shapes time perception. We show that context shifts, known to disrupt memory processing, also lead to robust contractions of perceived time. We discuss how both effects -- memory disruptions and time distortions -- may be linked via the hippocampus. "An hour, once it lodges in the queer element of the human spirit, may be stretched to fifty or a hundred times its clock length; on the other hand, an hour may be accurately represented on the timepiece of the mind by one second." -- Virginia Woolf

neuroscience↗

bioRxiv2021

Neural temporal context reinstatement of event structure during memory recall

Although life unfolds continuously, experiences are generally perceived and remembered as discrete events. Accumulating evidence suggests that event boundaries disrupt temporal representations and weaken memory associations. However, less is known about the consequences of event boundaries on temporal representations during retrieval, especially when temporal information is not tested explicitly. Using a neural measure of temporal context extracted from scalp electroencephalography, we found reduced temporal context similarity between studied items separated by an event boundary when compared to items from the same event. Further, while participants free recalled list items, neural activity reflected reinstatement of temporal context representations from study, including temporal disruption. A computational model of episodic memory, the Context Maintenance and Retrieval model (CMR; Polyn, Norman & Kahana, 2009), predicted these results, and made novel predictions regarding the influence of temporal disruption on recall order. These findings implicate the impact of event structure on memory organization via temporal representations.

neuroscience↗

bioRxiv2020

Survival of the salient: Emotion rescues otherwise forgettable memories via neural reactivation and post-encoding hippocampal connectivity

Emotions selective effects on memory go beyond the simple enhancement of threatening or rewarding stimuli. They can also rescue otherwise forgettable memories that share overlapping features. Here, we use functional magnetic resonance imaging (fMRI) to examine the brain mechanisms that support this retrograde memory enhancement. In a two-phase incidental encoding paradigm, participants first view images of neutral tools and animals. During Phase 1, these images are intermixed with neutral scenes, which provides a unique context tag for this specific phase of encoding. A few minutes later, during Phase 2, new pictures from one category are paired with a mild shock (fear-conditioned stimulus; CS+), while pictures from the other category are not shocked. fMRI analyses reveal that, across participants, retroactive memory benefits for Phase 1 CS+ items are associated with greater phasic reinstatement of the prior mental context during Phase 2 CS+ items. We also see that greater VTA/SN activation during Phase 2 CS+ items relates to this retroactive memory enhancement, suggesting that emotion promotes both the encoding and ongoing consolidation of overlapping representations. Additionally, we find that emotional experience-dependent changes in post-encoding hippocampal functional coupling with CS+ category-selective cortex relate to the magnitude of the retroactive memory effect. These hippocampal connectivity patterns also mediate the relationship between dopaminergic emotional encoding effects and across-participant variability in the retroactive memory benefit. Collectively, our findings suggest that an interplay between online and offline brain mechanisms may enable emotion to preserve seemingly mundane memories that become significant in the future.

neuroscience↗

bioRxiv2019

Dynamic arousal signals construct memories of time and events

Everyday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the brain mechanisms that support the transformation of continuous experience into memorable episodes remain unknown. Here we show that a sudden change in context, or event boundary, elicits a burst of autonomic arousal, as indexed by pupil dilation. These boundaries during dynamic experience also led to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the timing, order, and perceptual details of recent event sequences. Critically, we find that distinct cognitive components of this pupil response were associated with both subjective (temporal distance judgements) and objective (temporal order discrimination) measures of episodic memory, suggesting that multiple arousal-mediated cognitive processes help construct meaningful mnemonic events. Together, these findings reveal that arousal processes may play a fundamental role in everyday memory organization.

neuroscience↗

bioRxiv2019

Mnemonic prediction errors bias hippocampal states

In situations when our experience violates our predictions, it is adaptive to upregulate encoding of novel information, while down-weighting retrieval of erroneous memory predictions to promote an updated representation of the world. We asked whether mnemonic prediction errors promote distinct hippocampal processing states by leveraging recent results showing that encoding and retrieval processes are supported by distinct patterns of connectivity, or states, across hippocampal subfields. During fMRI scanning, participants were cued to retrieve well-learned room-images and were then presented with either an image identical to the learned room or a modified version (1-4 changes). We found that CA1-entorhinal connectivity increased, and CA1-CA3 connectivity decreased, with the number of changes to the learned rooms. Further, stronger memory predictions measured in CA1 during the cue correlated with the CA1-entorhinal connectivity increase in response to violations. Our findings provide a mechanism by which mnemonic prediction errors may drive memory updating - by biasing hippocampal states.

neuroscience↗