Biology subjects

Paller, K. A.

Publications and source records attributed to Paller, K. A..

15 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.

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bioRxiv2026

Depression symptoms are associated with affective neural processing during sleep and rest

Sleep supports offline information processing and is essential for cognitive and emotional functioning. Abnormal sleep patterns are a hallmark of affective disorders. We hypothesized that affective symptoms occur with maladaptive neural processing during offline periods. To test this idea, we used multivariate EEG decoding with cross-state classification. A model trained on EEG data acquired while participants (N = 52) viewed emotional images was used to classify stimulus valence. Applying this model to data collected during a nap revealed the re-emergence of affective neural patterns. Critically, offline reinstatement of patterns reflecting negatively valenced processing predicted greater depressive symptoms across participants. These associations reflected both cognitive-affective and somatic-performance depression subscales, and they generalized across sleep stages and wakeful rest. The finding that offline neural information processing is linked with emotional well-being supports a model whereby maladaptive negative biases can be perpetuated during rest, potentially shaping the progression of affective disorders.

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bioRxiv2025

Concurrent presentation of memory-related odors and sounds nullified sleep reactivation benefits

AbstractReactivation of recently acquired memories during sleep supports their longevity. Reactivation can be altered during sleep using odors or sounds through a technique termed targeted memory reactivation (TMR). Here, we attempted to selectively weaken memories by reactivating them together with forgetting instructions. We delivered sounds to reactivate spatial memories and concurrent odors to reactivate instructions. Participants learned about the instructions in a Directed-Forgetting task performed with a list of to-be-remembered and to-be-forgotten words. One odor was linked with instructions to forget, one with instructions to remember, and a third was not assigned any meaning. During a nap, sounds previously linked with object-location learning were simultaneously presented with these odors. Spatial recall was tested after sleep. Sound cues produced a selective recall benefit for weakly encoded memories. However, memory results did not support the prediction that forgetting could be instilled by the concurrent forget odor. An encoding-strength-dependent benefit was largest when sounds were presented together with the odor that lacked assigned meaning, whereas the other two odors both disrupted sound-induced memory reactivation. These two odors were linked with instructions and with multiple learning episodes in the Directed-Forgetting task. Accordingly, we infer that reactivation evoked by the remember and forget odor cues interfered with the reactivation of spatial memories. Odors also induced a prolonged decline in sigma EEG power (12-16 Hz) that continued at least 10 s after odor offset. Overall, these findings highlight the complexity of memory consolidation during sleep when multiple memories and multiple cues are involved.

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bioRxiv2023

Aversive memories can be weakened during human sleepvia the reactivation of positive interfering memories

Recollecting painful or traumatic experiences can be deeply troubling. Sleep may offer an opportunity to reduce such suffering. We developed a procedure to weaken older aversive memories by reactivating newer positive memories during sleep. Participants viewed 48 nonsense words each paired with a unique aversive image, followed by an overnight sleep. In the next evening, participants learned associations between half of the words and additional positive images, creating interference. During the following non-rapid-eye-movement sleep, auditory memory cues were unobtrusively delivered. Upon waking, presenting cues associated with both aversive and positive images during sleep, as opposed to not presenting cues, weakened aversive memory recall while increasing positive memory intrusions. Substantiating these memory benefits, computational modeling revealed that cueing facilitated evidence accumulation toward positive affect judgments. Moreover, cue-elicited theta brain rhythms during sleep predominantly predicted the recall of positive memories. A noninvasive sleep intervention can thus modify aversive recollection and affective responses. Significance StatementNot all memories are welcome: recollection and involuntary intrusions of aversive memories can be debilitating. Prior research shows that reactivating positive memories benefits psychological health, and memory reactivation can be externally triggered during human sleep. Here, we introduced a novel sleep-based memory updating procedure to weaken older aversive memories by reactivating newer positive memories. We found that such reactivation not only weakened the recall of aversive memories, but also increased involuntary intrusion of positive memories. Moreover, reactivation enhanced positive affect judgments. Our findings open new avenues for weakening aversive or traumatic memories during human sleep.

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bioRxiv2022

Context matters: Changes in memory over a period of sleep are driven by encoding context

During sleep, recently acquired episodic memories (i.e., autobiographical memories for specific events) are strengthened and transformed, a process termed consolidation. These memories are contextual in nature, with details of specific features interwoven with more general properties such as the time and place of the event. In this study, we hypothesized that the context in which a memory is embedded would guide the process of consolidation during sleep. To test this idea, we employed a spatial memory task and considered changes in memory over a 10-hour period including either sleep or wake. In both conditions, participants (N = 62) formed stories that contextually bound four objects together, and then encoded the on-screen spatial position of all objects. Results showed that the changes in memory over the sleep period were correlated among contextually linked objects, whereas no such effect was identified for the wake group. These results suggest that contexts binding different memories together play an active role in consolidation during sleep.

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bioRxiv2022

Improving Memory via Automated Targeted Memory Reactivation during Sleep

A widely accepted view in memory research is that previously acquired information can be reactivated during sleep, leading to persistent memory storage. Recently, Targeted Memory Reactivation (TMR) has been developed as a technique whereby specific memories can be reactivated during sleep using a sensory stimulus linked to prior learning. TMR can improve various types of memory, raising the possibility that it may be useful for cognitive enhancement and clinical therapy. A major challenge for the expanded use of TMR is that experimenters must manually control stimulation timing and intensity, which is impractical in most settings. To address this limitation, we developed the SleepStim system for automated TMR in the home environment. SleepStim includes a smartwatch to collect movement and heart-rate data, plus a smartphone to emit auditory cues. A machine-learning model identifies periods of deep non-REM sleep and triggers TMR sounds within these periods. We tested whether this system could replicate the spatial-memory benefit of in-lab TMR. Participants learned the locations of objects on a grid, and then half of the object locations were reactivated during sleep over three nights. In an experiment with 61 participants, the TMR effect was nonsignificant but varied systematically with stimulus intensity; low-intensity but not high-intensity stimuli produced memory benefits. In a second experiment with 24 participants, we limited stimulus intensity and found that TMR reliably improved spatial memory, consistent with effects observed in laboratory studies. We conclude that SleepStim can effectively accomplish automated TMR and that avoiding sleep disruption is critical for TMR benefits.

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bioRxiv2022

Electrophysiological Markers of Memory Consolidation in the Human Brain when Memories are Reactivated during Sleep

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states, and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly, but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10-20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage. Significance StatementSleep contributes to memory consolidation, we presume, because memories are replayed during sleep. Understanding this aspect of consolidation can help with optimizing normal learning in many contexts, and with treating memory disorders and other diseases. Here, we systematically manipulated sleep-based processing using targeted memory reactivation; brief sounds coupled with pre-sleep learning were quietly presented again during sleep, producing (a) recall improvements for specific spatial memories associated with those sounds, and (b) physiological responses in the sleep EEG. Neural activity in the hippocampus and adjacent medial temporal cortex was thus found in association with memory consolidation during sleep. These findings advance understanding of consolidation by linking beneficial memory changes during sleep to both memory reactivation and specific patterns of brain activity.

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bioRxiv2022

Sleep Disruption Selectively Weakens Reactivated Memories

A widely accepted view in memory research is that recently stored information can be reactivated during sleep, leading to memory strengthening. Two recent studies have shown this effect can be reversed in participants with highly disrupted sleep. To test whether weakening of reactivated memories can result directly from sleep disruption, in this experiment we varied the intensity of memory reactivation cues, such that some produced sleep arousals. Prior to sleep, participants (local community members) learned the locations of 75 objects, each accompanied by a sound naturally related to that object. Location recall was tested before and after sleep, and a subset of the sounds were presented during sleep. Reactivation with arousal weakened memories, unlike the improvement typically found. We conclude that reactivated memories can be selectively weakened during sleep, and that memory reactivation may strengthen or weaken memories depending on additional factors such as concurrent sleep disruption. Statement of RelevanceThe results of this study have implications for both human health and basic psychology. Sleep disorders like apnea are associated with memory problems; our results suggest a possible mechanism where frequent arousal may disrupt the naturally occurring reactivation of memory in sleep. These results also highlight the importance of avoiding brief sleep disruption for good sleep hygiene. Finally, we raise the possibility that reactivation with sleep disruption could be used therapeutically to weaken distressing memories. Our observation that memories can also be either weakened or strengthened by sleep reactivation has implications for understanding the mechanisms of memory consolidation. In particular, we suggest that sleep memory reactivation may be a reconsolidation-like process with memory restabilization required after reactivation. Our findings also suggest avenues for future experiments; such as using sleep disruption to study the time course of memory reactivation.

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bioRxiv2022

Made together, replayed together: Context reinstatement during sleep guides memory consolidation

New memories arent quarantined from each other when first encoded; rather, they are interlinked with memories that were encoded in temporal proximity or share semantic features. By selectively biasing memory processing during sleep, here we test whether context influences sleep-consolidation. Participants first formed 18 idiosyncratic narratives, each linking four objects together. Before sleep,they also memorized an on-screen position for each object. During sleep, 12 object-specific sounds were unobtrusively presented, thereby cuing the corresponding spatial memories and impacting spatial recall as a function of initial memory strength. As hypothesized, we find that recall for non-cued objects contextually linked with cued objects also changed. Post-cue electrophysiological responses suggest that activity in the sigma band supports context reinstatement and predicts context-related memory benefits. Concurrently, context-specific electrophysiological activity patterns emerge during sleep. We conclude that reactivation of individual memories during sleep evokes reinstatement of their context, thereby impacting consolidation of associated knowledge.

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bioRxiv2021

Reactivating Memories from a Mathematical Task over a Period of Sleep

Sleep, especially slow-wave sleep (SWS), has been found to facilitate memory consolidation for many types of learning. Mathematical learning, however, has seldom been examined in this context. Solving multiplication problems involves multiple steps before problems can be mastered or answers memorized, and thus it can depend on both skill learning and fact learning. Here we aimed to test the hypothesis that memory reactivation during sleep contributes to multiplication learning. To do so, we used a technique known as targeted memory reactivation (TMR), or the pairing of newly learned information with specific stimuli that are later presented during sleep. With TMR, specific memories can be reactivated over a period of sleep without disrupting ongoing sleep. We applied TMR during an afternoon nap to reactivate half of the multiplication problems that had previously been practiced. Results showed no effect of TMR on response time or accuracy of multiplication problem solving. Because these results were unexpected, we also used a variation of this paradigm to examine results in subjects who remained awake. Comparisons between the wake and sleep groups showed no difference in response time or accuracy in either the initial test or the final test. Although neither TMR nor sleep differentially influenced multiplication performance, correlational analysis provided some clues about mathematical problem solving and sleep. On the basis of these findings, even though they did not provide convincing support for our hypotheses, we suggest future experiments that could help produce a better understanding of the relevance of sleep and memory reactivation for this type of learning.

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bioRxiv2021

Targeted Memory Reactivation of Face-Name LearningDepends on Ample and Undisturbed Slow-Wave Sleep

Face memory, including the ability to recall the name of a familiar person, is often crucial in social interactions, and like many other memory functions, it may rely on sleep. We investigated whether targeted memory reactivation during sleep could improve associative and perceptual aspects of face memory. Participants studied 80 face-name pairs, and then a subset of spoken names was presented unobtrusively during a daytime nap. This reactivation preferentially improved recall for those face-name pairs, as modulated by two factors related to sleep quality. That is, the memory benefit was positively correlated with the duration of stage N3 sleep (slow-wave sleep) and with the extent to which cues presented during SWS did not produce a sleep disruption indexed by increased alpha-band electroencephalographic activity in the 5 seconds after a cue. Follow-up analyses showed that a memory benefit from presenting spoken names during sleep was evident in participants with high amounts of SWS or with low amounts of sleep disruption. We conclude that sleep reactivation can strengthen memory for specific face-name associations and that the effectiveness of reactivation depends on uninterrupted N3 sleep.

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bioRxiv2020

Dynamics of nonlinguistic statistical learning: From neural entrainment to the emergence of explicit knowledge

Humans are highly attuned to patterns in the environment. This ability to detect environmental patterns, referred to as statistical learning, plays a key role in many diverse aspects of cognition. However, the spatiotemporal neural mechanisms underlying implicit statistical learning, and how these mechanisms may relate or give rise to explicit learning, remain poorly understood. In the present study, we investigated these different aspects of statistical learning by using an auditory nonlinguistic statistical learning paradigm combined with magnetoencephalography. Twenty-four healthy volunteers were exposed to structured and random tone sequences, and statistical learning was quantified by neural entrainment. Already early during exposure, participants showed strong entrainment to the embedded tone patterns. A significant increase in entrainment over exposure was detected only in the structured condition, reflecting the trajectory of learning. While source reconstruction revealed a wide range of brain areas involved in this process, entrainment in areas around the left pre-central gyrus as well as right temporo-frontal areas significantly predicted behavioral performance. Sensor level results confirmed this relationship between neural entrainment and subsequent explicit knowledge. These results give insights into the dynamic relation between neural entrainment and explicit learning of triplet structures, suggesting that these two aspects are systematically related yet dissociable. Neural entrainment reflects robust, implicit learning of underlying patterns, whereas the emergence of explicit knowledge, likely built on the implicit encoding of structure, varies across individuals and may depend on factors such as sufficient exposure time and attention.

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bioRxiv2018

Targeted memory reactivation during sleep elicits neural signals related to learning content

Reactivation of learning-related neural activity patterns is thought to drive memory stabilization. However, finding reliable, non-invasive, content-specific indicators of reactivation remains a central challenge. Here, we attempted to decode the content of reactivated memories in the electroencephalogram (EEG) during sleep. During encoding, human participants learned to associate spatial locations of visual objects with left- or right-hand movements, and each object was accompanied by an inherently related sound. During subsequent slow-wave sleep within an afternoon nap, we presented half of the sound cues that were associated (during wake) with left- and right-hand movements before bringing participants back for a final post-nap test. We trained a classifier on sleep EEG data (focusing on lateralized EEG features that discriminated left- vs. right-sided trials during wake) to predict learning content when we reactivated the memories during sleep. Discrimination performance was significantly above chance and predicted subsequent memory, supporting the idea that reactivation leads to memory stabilization. Moreover, these lateralized signals increased with post-cue spindle power, demonstrating that reactivation has a strong relationship with spindles. These results show that lateralized activity related to individual memories can be decoded from sleep EEG, providing an effective indicator of offline reactivation.

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bioRxiv2018

Targeted memory reactivation during sleep to strengthen memory for arbitrary pairings

A powerful way to investigate memory consolidation during sleep utilizes acoustic stimulation to reactivate memories. In multiple studies, Targeted Memory Reactivation (TMR) using sounds associated with prior learning improved later memory, as in recalling locations where objects previously appeared. In the present experiment, we examined whether a variant of the same technique could strengthen memory for the locations of pairs of objects. Each sound was naturally connected to one object from each pair, but we hypothesized that both memories could be improved with TMR. We first asked participants to memorize each of 50 pairs of objects by associating the two objects with each other and with the sound of one of the objects (e.g., cat-meow). Next, objects were presented in unique locations on a grid. Participants learned these locations in an adaptive procedure. During an afternoon nap, 25 of the sounds were quietly presented. In memory tests given twice before and twice after the nap, participants heard the sound for each object pair and were asked to recall the name of the second object and the locations of both objects. Forgetting scores were calculated using the mean difference between pre-nap and post-nap spatial recall errors. We found less forgetting after the nap for cued compared to non-cued objects. Additionally, the extent of forgetting tended to be similar for the two members of each pair, but only for cued pairs. Results thus substantiate the potential for sounds to reactivate spatial memories during sleep and thereby improve subsequent recall performance, even for multiple objects associated with a single sound and when participants must learn a novel sound-object association.\n\nHighlightsO_LIMemories can be improved during sleep using arbitrary sounds\nC_LIO_LIParticipants learned a random screen location for each of 100 objects\nC_LIO_LIObjects were learned in pairs with the characteristic sound of one of the objects\nC_LIO_LIHalf of those sounds were presented during a nap that followed learning\nC_LIO_LIAfter sleep, location recall was more accurate for cued than for non-cued objects\nC_LI

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bioRxiv2017

Sleep spindle refractoriness segregates periods of memory reactivation

The stability of long-term memories is enhanced by reactivation during sleep. Correlative evidence has linked memory reactivation with thalamocortical sleep spindles, although their functional role is poorly understood. Our initial study replicated this correlation but also demonstrated a novel rhythmicity to spindles, such that spindles are less likely to occur immediately following other spindles. We leveraged this rhythmicity to test the role of spindles in memory by using real-time spindle tracking to present cues inside versus outside the presumptive refractory period; as predicted, cues presented in the refractory period led to better memory. Our findings reveal a previously undescribed neural mechanism whereby spindles segment sleep into two distinct substates: prime opportunities for reactivation and gaps that segregate reactivation events.\n\nOne Sentence SummaryThe characteristic timing of sleep spindles regulates when memories can be reactivated during sleep.

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