Subsequent Memory Research Articles

Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation.

When retrieved, seemingly stable memories can become sensitive to significant events, such as acute stress. The mechanisms underlying these memory dynamics remain poorly understood. Here, we show that noradrenergic stimulation after memory retrieval impairs subsequent remembering, depending on hippocampal and cortical signals emerging during retrieval. In a three-day study, we measured brain activity using fMRI during initial encoding, 24 hr-delayed memory cueing followed by pharmacological elevations of glucocorticoid or noradrenergic activity, and final recall. While post-retrieval glucocorticoids did not affect subsequent memory, the impairing effect of noradrenergic arousal on final recall depended on hippocampal reactivation and category-level reinstatement in the ventral temporal cortex during memory cueing. These effects did not require a reactivation of the original memory trace and did not interact with offline reinstatement during rest. Our findings demonstrate that, depending on the retrieval-related neural reactivation of memories, noradrenergic arousal after retrieval can alter the future accessibility of consolidated memories.

Mapping patterns of thought onto brain activity during movie-watching.

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the 'here and now' depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better-on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi-modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films.

Reactivation and consolidation of memory traces during post-encoding rest across the adult lifespan.

Episodic memory is a critical cognitive function that enables the encoding, storage, and retrieval of new information. Memory consolidation, a key stage of episodic memory, stabilizes this newly encoded information into long-lasting brain "storage." Studies using fMRI to investigate post-encoding awake rest holds promise to shed light on early, immediate consolidation mechanisms. Here, we review fMRI studies during episodic memory to document common methods to investigate post-encoding consolidation, such as multivoxel pattern analysis (MVPA) and functional connectivity, and the current state of the science in both healthy younger and older adults. In young adults, post-encoding reactivation of stimuli-specific neural patterns in the hippocampus and its connectivity with cortical and subcortical areas (e.g., visual-temporal cortex, medial prefrontal, and medial parietal cortex) correlate with subsequent memory performance. Conversely, studies in older adults highlight the importance of large-scale brain networks during post-encoding rest, particularly the default mode network (DMN). Alterations in connectivity between the DMN and task-positive networks may help older adults maintain episodic memory. Furthermore, non-invasive brain stimulation techniques can enhance these post-encoding consolidation processes and improve memory performance in both younger and older adults. Notably, a lack of studies has investigated post-encoding memory consolidation in neurodegenerative disorders. This review underscores the importance of understanding how post-encoding neural reactivation and connectivity evolve with age to partially explain age-related declines in episodic memory performance and how such declines can be restored.

Pattern integration and differentiation: dual process model of episodic memory

Abstract The role of precise timing in episodic memory remains obscure. We showed 139 participants episodes consisting of objects, and tested subsequent memory for the precise timing and order of the objects and episodes. Temporal compression of the episode enhanced memory for relative but not absolute timing of the objects’ presentation and their order. Conversely, temporal expansion between neighboring episodes was associated with successful memory for episode order. fMRI in 36 participants revealed that temporal compression of the episode was associated with more similar activation patterns within episodes in several brain regions including the posterior hippocampus. On the other hand, the activation pattern in the anterior hippocampus and other brain regions became more unique with temporal expansion between neighboring episodes. We propose that human episodic memory relies on two fundamentally opposite processes; pattern integration helps strengthen the relationship between the items that make up an episode, and pattern differentiation keeps different episodes apart.

Studying Pupil-Size Changes as a Function of Task Demands and Emotional Content in a Clinical Interview Situation

The human pupil changes size in response to processing demands or cognitive (work)load and emotional processing. Therefore, it is important to test if automatic tracking of cognitive load by pupil-size measurement is possible under conditions of varying levels of emotion-related processing. Here, we investigated this question in an experiment simulating a highly relevant applied context in which cognitive load and emotional processing can vary independently: a clinical interview. Our participants conducted a live clinical interview via computer monitor with a confederate as an interviewee. We used eye-tracking and automatic extraction of participants’ pupil size to monitor cognitive load (single vs. dual tasks, between participants), while orthogonally varying the emotional content of the interviewee’s answers (neutral vs. negative, between participants). We ensured participants’ processing of the verbal content of the interview by asking all participants to report on the content of the interview in a subsequent memory test and by asking them to discriminate if the answers of the interviewee referred to only herself or to somebody else (too). In the dual-task condition, participants had to monitor additionally if the facial emotional expressions of the interviewee matched the content of her verbal responses. Results showed that pupil-size extraction reliably discriminated between high and low cognitive load, albeit to a lower degree under negative emotional content conditions. This was possible with an algorithmic online measure of cognitive load as well as with a conventional pupil-size measure, providing proof of the external validity of the algorithm/online measure.

The effect of instructed refreshing on working memory: Is the memory boost a function of refreshing frequency or refreshing duration?

AbstractRefreshing is assumed to reactivate the contents of working memory in an attention-based way, resulting in a boost of the attended representations and hence improving their subsequent memory. Here, we examined whether the refreshing-induced memory boost is a constant or a gradual, time-dependent phenomenon. If the beneficial effect of refreshing on memory performance is due to the information being selected for refreshing (i.e., selection hypothesis), a constant memory boost is expected to occur each time an item is selected for refreshing, with better memory performance for items that are selected more often. If, however, the beneficial effect of refreshing on memory performance is due to spending time in the focus of attention during refreshing (i.e., duration hypothesis), a gradual memory boost is expected, with the size of the memory boost being a direct function of how long the item has been the object of focused attention. To distinguish between these hypotheses, we instructed and guided the use of refreshing during retention through the presentation of cues, and varied the number of refreshing steps and their duration independently. The number of refreshing steps, but not their duration, had an effect on recall, in agreement with the selection hypothesis. However, some of the results were less robust than anticipated, indicating that the effect of instructed refreshing is limited to certain task parameters.

Subsequent Memory Effects in Cortical Pattern Similarity Differ by Semantic Class.

Although living and nonliving stimuli are known to rely on distinct brain regions during perception, it is largely unknown if their episodic memory encoding mechanisms differ as well. To investigate this issue, we asked participants to encode object pictures (e.g., a picture of a tiger) and to retrieve them later in response to their names (e.g., word "tiger"). For each of four semantic classes (living-animate, living-inanimate, nonliving-large, and nonliving-small), we examined differences in the similarity in activation patterns (neural pattern similarity [NPS]) for subsequently remembered versus forgotten items. Higher NPS for remembered items suggests an advantage of within-class item similarity, whereas lower NPS for remembered items indicates an advantage for item distinctiveness. We expect NPS within class-specific regions to be higher for remembered than for forgotten items. For example, the parahippocampal cortex has a well-known role in scene processing [Aminoff, E. M., Kveraga, K., & Bar, M. The role of the parahippocampal cortex in cognition. Trends in Cognitive Sciences, 17, 379-390, 2013], and the anterior temporal and inferior frontal gyrus have well-known roles in object processing [Clarke, A., & Tyler, L. K. Object-specific semantic coding in human perirhinal cortex. Journal of Neuroscience, 34, 4766-4775, 2014]. As such, we expect to see higher NPS for remembered items in these regions pertaining to scenes and objects, respectively. Consistent with this hypothesis, in fusiform, parahippocampal, and retrosplenial regions, higher NPS predicted memory for subclasses of nonliving objects, whereas in the left inferior frontal and left retrosplenial regions, lower NPS predicted memory for subclasses of living objects. Taken together, the results support the idea that subsequent memory depends on a balance of similarity and distinctiveness and demonstrate that the neural mechanisms of episodic encoding differ across semantic categories.

How predictability and individual alpha frequency shape memory: Insights from an event-related potential investigation

Prediction and memory are strongly intertwined, with predictions relying on memory retrieval, whilst also influencing memory encoding. However, it is unclear how predictability influences explicit memory performance, and how individual neural factors may modulate this relationship. The current study sought to investigate the effect of predictability on memory processing with an analysis of the N400 event-related potential in a context extending beyond language. Participants (N = 48, females = 33) completed a study-test paradigm where they first viewed predictable and unpredictable four-item ‘ABCD’ sequences of outdoor scene images, whilst their brain activity was recorded using electroencephalography. Subsequently, their memory for the images was tested, and N400 patterns during learning were compared with memory outcomes. Behavioural results revealed better memory for images in predictable sequences in contrast to unpredictable sequences. Memory was also strongest for predictable images in the ‘B’ position, suggesting that when processing longer sequences, the brain may prioritise the data deemed most informative. Strikingly, greater N400 amplitudes during learning were associated with enhanced memory at test for individuals with low versus high individual alpha frequencies. In light of the relationship between the N400 and stimulus predictability, this finding may imply that predictive processing differs between individuals to influence the extent of memory encoding. Finally, exploratory analyses provided evidence for a later positivity that was predictive of subsequent memory performance. Ultimately, the results highlight the complex and interconnected relationship between predictive processing and memory, whilst shedding light on the accumulation of predictions across longer sequences.

Attention and the forward testing effect.

Memory retrieval affects subsequent memory in both positive (e.g., the testing effect) and negative (e.g., retrieval-induced forgetting [RIF]) ways, and can be contrasted with other forms of memory modification (e.g., study-based encoding). Divided attention substantially impairs study-based encoding but has a modest effect on retrieval. What of the subsequent learning consequences of retrieval? Earlier studies indicate that certain positive effects (i.e., the testing effect) are not reduced by distraction, whereas negative effects (i.e., RIF) are eliminated. The present study assessed an indirect (positive) effect of retrieval-the forward testing effect (FTE), in which prior retrieval or retrieval attempts enhance subsequent learning. Two experiments examined the role of attention in both the standard FTE and the pretesting effect. In Experiment 1, participants learned three study lists through retrieval practice or restudy, followed by a fourth study list. Prior retrieval practice enhanced subsequent new learning more than restudy (i.e., the standard FTE), and to a similar degree under full attention (FA) and divided attention (DA). In Experiment 2, participants learned cue-target word pairs by either studying the pair or guessing the target when shown a cue (i.e., pretesting) followed by the correct pair. Pretesting enhanced memory more than just studying to a similar degree under FA and DA. In sum, both forms of the FTE were unaffected by distraction, indicating that these positive consequences of retrieval are not based on controlled processes but instead appear to be relatively obligatory consequences of retrieval (or retrieval attempts). These results also have relevance for specific accounts of the standard FTE and the pretesting effect.

Time after Time: Preserving Temporal Memories When Experiences Repeat.

Remembering when events occur in time is fundamental to episodic memory. Yet, many experiences repeat over time creating the potential for interference when attempting to recall temporally specific memories. Here, we argue that temporal memories are protected, in part, by reinstatement of temporal context information that is triggered by stimulus repetitions. We motivate this argument by integrating seminal findings across several distinct literatures and methodologies. Specifically, we consider key insights from foundational behavioral studies of temporal memory, recent electrophysiological and neuroimaging approaches to measuring memory reinstatement, and computational models that describe how temporal context representations shape memory processes. We also note several open questions concerning how temporal context reinstatement might influence subsequent temporal memory, including potential mediating effects of event spacing and event boundaries. These ideas and questions have the potential to guide future research and, ultimately, to advance theoretical accounts of how we preserve temporal memories.

Limited carry-over effects of socioemotional manipulations on subsequent unrelated memory tasks.

Although age is typically associated with significant impairments in memory performance, several domains exist in which these impairments are reduced or even eliminated. These "pockets of preservation" in older adults' memory can be seen in tasks involving socioemotional processing and may be supported by distinct encoding or retrieval modes relative to neutral content. The current study examines whether engaging in socioemotional tasks prior to encoding or retrieval allows older adults to enter an encoding or retrieval mode that better supports memory performance. In two online studies, adults across the lifespan were asked to complete a memory task where they incidentally encoded and retrieved neutral (Experiment 1, N = 1621) or emotional (Experiment 2, N = 409) word-image pairs. Participants were randomly assigned to a control (i.e., no manipulation), pre-encoding, or pre-retrieval socioemotional manipulation condition. There were no main effects of manipulation condition, suggesting that such manipulations may not reliably enhance memory. However, future research is needed to follow up on exploratory analyses that highlighted particular conditions under which these manipulations may convey benefits. There were also no age-by-manipulation interactions. While these null effects may suggest that these manipulations are not better suited to older adults, this may also be a result of the unexpected age-related increases (Experiment 1) and age invariance (Experiment 2) in overall memory accuracy in the current study. Socioemotional manipulations should also be examined in older adults who underperform younger adults.

A default mode network subsystem supports both item and associative word encoding: Insights from a meta-analysis

Abstract Recent meta-analytic evidence has underscored the significant role of the default mode network (DMN) in facilitating item word encoding. This study builds on this finding through a comprehensive meta-analysis of fMRI-based subsequent memory studies that use words as stimuli. The results highlight several key functions within the DMN. Firstly, the dorsomedial prefrontal cortex (dmPFC) subsystem of the DMN plays a pivotal role in enhancing successful word encoding, suggesting its vital involvement in the semantic processing of incoming verbal information. Secondly, the utility of the dmPFC subsystem extends beyond item word encoding to associative word encoding tasks, demonstrating its broad applicability in verbal information encoding. Thirdly, regions within the left inferior frontal cortex, a core component of the dmPFC subsystem, show increased activity during associative compared to item word encoding, emphasizing their role in integrating verbal information with contextual details. Contrary to previous research that linked the DMN with encoding interference—often attributed to the core subsystem’s tendency for mind-wandering—this study highlights the facilitative role of the dmPFC subsystem in memory encoding. The contrasting roles of the DMN subsystems, both interfering and facilitating, challenge traditional views and advocate for a more nuanced understanding of the network’s role in memory encoding.

Pattern separation during encoding and Subsequent Memory Effect

Memory retrieval has been extensively studied in relation to the encoding processes that precede access to stored information. Event related potentials (ERP) research has compared brain potentials elicited during the study phase of successful and unsuccessful retrieval, finding greater activation for the subsequent retrieval information. In this work we were interested in exploring the neural markers associated to subsequent recognition when similar memories are subsequently encoded. We used a Subsequent Memory paradigm in which we manipulated the number of similar items within a category (2 or 6) that participants encoded. Manipulating the number of similar encoded items within a category allowed us to test whether encoding markers of subsequent recognition depend solely on memory trace strength or, on the contrary, successful recognition is influenced by subsequently presented similar memories, and consequently may not be reflected in higher activation in such cases. After a 20-minute period, participants performed a recognition task providing one of a three-option judgement: “old”, “similar” and “new”, which allowed us to test if the amplitude of ERP waveforms varied based on the similarity judgement of the unrecognized encoded item. We did not observe a significant parietal subsequent memory effect, however, old hits and similar false alarms were both significantly different from similar correct rejections and old false alarms in ERP retrieval. These findings suggest that differences in brain responses between conditions are specifically related to the retrieval process and not the encoding process, indicating potential differential effects on memory during retrieval. Moreover, it is also possible that differences in brain responses develop or change over the rest time between phases, influencing how these conditions manifest across different stages of information processing.

Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus

Working memory (WM) and long-term memory (LTM) are often viewed as separate cognitive systems. Little is known about how these systems interact when forming memories. We recorded single neurons in the human medial temporal lobe while patients maintained novel items in WM and completed a subsequent recognition memory test for the same items. In the hippocampus, but not in the amygdala, the level of WM content-selective persistent activity during WM maintenance was predictive of whether the item was later recognized with high confidence or forgotten. By contrast, visually evoked activity in the same cells was not predictive of LTM formation. During LTM retrieval, memory-selective neurons responded more strongly to familiar stimuli for which persistent activity was high while they were maintained in WM. Our study suggests that hippocampal persistent activity of the same cells supports both WM maintenance and LTM encoding, thereby revealing a common single-neuron component of these two memory systems.

Emotional future simulations: neural and cognitive perspectives.

LeDoux's work on the emotional brain has had broad impact in neuroscience and psychology. Here, we discuss an aspect of the emotional brain that we have examined in our laboratory during the past two decades: emotional future simulations or constructed mental representations of positive and negative future experiences. Specifically, we consider research concerning (i) neural correlates of emotional future simulations, (ii) how emotional future simulations impact subsequent cognition and memory, (iii) the role of emotional future simulations in worry and anxiety, and (iv) individual differences in emotional future simulation related to narcissistic grandiosity. The intersection of emotion and future simulation is closely linked to some of LeDoux's primary scientific concerns.

Long-term retention of real-world experiences in a patient with profound amnesia

The medial temporal lobe (MTL) is known to be critical for healthy memory function, but patients with MTL damage can, under certain circumstances, demonstrate successful learning of novel information encountered outside the laboratory. Here, we describe a patient, D.C., with extensive but focal bilateral MTL damage centering primarily on his hippocampus, whose memory for real-world experiences was assessed. Tests of remote memory indicated at least some capacity to retrieve specific details. To test his anterograde memory, he was taken on a tour of the NIH Clinical Center, with unique events occurring at each of ten specific locations. His memory for these events was tested after 1 h, and again after fifteen months. Initially, D.C. could not recall having participated in the tour, even when cued with photographs of specific places he had visited. However, he achieved 90% accuracy on a forced choice recognition test of old and new objects he encountered on the tour, and his recognition of these objects remained intact over a year later when he was tested once again. Subsequent recognition memory tests using novel picture stimuli in a standard laboratory-style computer task resulted in chance-level performance across multiple test formats and stimulus categories. These findings suggest a potentially privileged role for natural learning for long-term retention in a patient with severely damaged medial temporal lobes.

Transient susceptibility to interference at event boundaries impacts long-term memory of naturalistic episodes

ABSTRACT During ongoing narratives, event boundaries trigger processes relevant for subsequent memory. Previous work has shown that novel, unrelated input presented at an event boundary can retroactively interfere with short-term retention of the preceding event. This interference was attributed to a perturbation of offset-related processes taking place within seconds after encoding and supporting the binding of elements into a coherent event memory. However, the temporal specificity of this memory interference and whether its impact extends to longer retention delays has not been addressed. Here, participants viewed either individual or pairs of short narrative movie clips. Susceptibility to interference at event boundaries was probed by presenting the second clip either immediately after the first, or with a 2s encoding delay. In free and cued recall, after 20 min and 24 h, only memory for movie clips that were immediately followed by a second clip was reduced compared to clips shown in isolation. Intact offset-related processes (as indexed by successful recall of the first movie) did not negatively affect encoding of the subsequent clip. Together, these results indicate that the 2s time-window immediately after an event is relevant for successful consolidation and long-term retention of memory.

Polysomnographically mediated cognitive improvements in individuals with insomnia symptoms following continuous theta-burst stimulation of the default mode network

IntroductionInsomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both.MethodData presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography.ResultsSlow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090).ConclusionsFindings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period.Clinical trial registrationThis study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&country=United%20States&state=Arizona&cond=insomnia&intr=tms%20&rank=1

Radiosensitivity-related Variation in MicroRNA-34a-5p Levels and Subsequent Neuronal Loss in the Hilus of the Dentate Gyrus after Irradiation at Postnatal Days 10 and 21 in Mice.

The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.

Rhythmic Temporal Cues Coordinate Cross-frequency Phase-amplitude Coupling during Memory Encoding.

Accumulating evidence suggests that rhythmic temporal cues in the environment influence the encoding of information into long-term memory. Here, we test the hypothesis that these mnemonic effects of rhythm reflect the coupling of high-frequency (gamma) oscillations to entrained lower-frequency oscillations synchronized to the beat of the rhythm. In Study 1, we first test this hypothesis in the context of global effects of rhythm on memory, when memory is superior for visual stimuli presented in rhythmic compared with arrhythmic patterns at encoding [Jones, A., & Ward, E. V. Rhythmic temporal structure at encoding enhances recognition memory, Journal of Cognitive Neuroscience, 31, 1549-1562, 2019]. We found that rhythmic presentation of visual stimuli during encoding was associated with greater phase-amplitude coupling (PAC) between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. In Study 2, we next investigated cross-frequency PAC in the context of local effects of rhythm on memory encoding, when memory is superior for visual stimuli presented in-synchrony compared with out-of-synchrony with a background auditory beat (Hickey et al., 2020). We found that the mnemonic effect of rhythm in this context was again associated with increased cross-frequency PAC between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. Furthermore, the magnitude of gamma power modulations positively scaled with the subsequent memory benefit for in- versus out-of-synchrony stimuli. Together, these results suggest that the influence of rhythm on memory encoding may reflect the temporal coordination of higher-frequency gamma activity by entrained low-frequency oscillations.