Distinct encoding and post-encoding representational formats contribute to episodic sequence memory formation.

In episodic encoding, an unfolding experience is rapidly transformed into a memory representation that binds separate episodic elements into a memory form to be later recollected. However, it is unclear how brain activity changes over time to accommodate the encoding of incoming information. This study aimed to investigate the dynamics of the representational format that contributed to memory formation of sequential episodes. We combined representational similarity analysis and multivariate decoding approaches on EEG data to compare whether "category-level" or "item-level" representations supported memory formation during the online encoding of a picture triplet sequence and offline, in the period that immediately followed encoding. The findings revealed a gradual integration of category-level representation during the online encoding of the picture sequence and a rapid item-based neural reactivation of the encoded sequence at the episodic offset. However, we found that only memory reinstatement at episodic offset was associated with successful memory retrieval from long-term memory. These results suggest that post-encoding memory reinstatement is crucial for the rapid formation of unique memory for episodes that unfold over time. Overall, the study sheds light on the dynamics of representational format changes that take place during the formation of episodic memories.

Contextual incongruency triggers memory reinstatement and the disruption of neural stability.

Schemas, or internal representation models of the environment, are thought to be central in organising our everyday life behaviour by giving stability and predictiveness to the structure of the world. However, when an element from an unfolding event mismatches the schema-derived expectations, the coherent narrative is interrupted and an update to the current event model representation is required. Here, we asked whether the perceived incongruence of an item from an unfolding event and its impact on memory relied on the disruption of neural stability patterns preceded by the neural reactivation of the memory representations of the just-encoded event. Our study includes data from two different experiments whereby human participants (N = 33, 26 females and N = 18, 16 females, respectively) encoded images of objects preceded by trial-unique sequences of events depicting daily routine. We found that neural stability patterns gradually increased throughout the ongoing exposure to a schema-consistent episode, which was corroborated by the re-analysis of data from two other experiments, and that the brain stability pattern was interrupted when the encoding of an object of the event was incongruent with the ongoing schema. We found that the decrease in neural stability for low-congruence items was seen at ∼1000 ms from object encoding onset and that it was preceded by an enhanced N400 ERP and an increased degree of neural reactivation of the just-encoded episode. Current results offer new insights into the neural mechanisms and their temporal orchestration that are engaged during online encoding of schema-consistent episodic narratives and the detection of incongruencies.

Gamma amplitude is coupled to opposed hippocampal theta-phase states during the encoding and retrieval of episodic memories in humans.

Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40-140 Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying hippocampal theta rhythm (4-9 Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented, and 24 h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants' memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.

Authority Brings Responsibility: Feedback from Experts Promotes an Overweighting of Health-Related Pseudoscientific Beliefs.

The popularity and spread of health-related pseudoscientific practices is a worldwide problem. Despite being counteracted by competent agents of our societies, their prevalence and spread continue to grow. Current research has focused on identifying which characteristics make us more likely to hold pseudoscientific beliefs. However, how we hold these beliefs despite all the available information against them is a question that remains unanswered. Here, we aimed to assess if the development of health-related pseudoscientific beliefs could be driven by a positive bias in belief updating. Additionally, we aimed to explore whether this bias could be exacerbated, depending on source credibility. In this study, participants (N = 116) underwent a belief updating task where they offered their agreement with various health-related pseudoscientific statements before and after receiving supporting and discrediting feedback from (a) experts (doctors), (b) peers, or (c) a random number generator. Our results suggest that when receiving feedback from experts (but not from peers or random feedback), the participants preferentially integrated supporting information relative to discrediting information about health-related pseudoscience. We discuss the implications of this biased belief updating pattern on health-related pseudoscientific research and suggest new strategies for intervention focused on increasing awareness, training, and consensus among healthcare practitioners.

Post-encoding Reactivation Is Related to Learning of Episodes in Humans.

Prior animal and human studies have shown that post-encoding reinstatement plays an important role in organizing the temporal sequence of unfolding episodes in memory. Here, we investigated whether post-encoding reinstatement serves to promote the encoding of "one-shot" episodic learning beyond the temporal structure in humans. In Experiment 1, participants encoded sequences of pictures depicting unique and meaningful episodic-like events. We used representational similarity analysis on scalp EEG recordings during encoding and found evidence of rapid picture-elicited EEG pattern reinstatement at episodic offset (around 500 msec post-episode). Memory reinstatement was not observed between successive elements within an episode, and the degree of memory reinstatement at episodic offset predicted later recall for that episode. In Experiment 2, participants encoded a shuffled version of the picture sequences from Experiment 1, rendering each episode meaningless to the participant but temporally structured as in Experiment 1, and we found no evidence of memory reinstatement at episodic offset. These results suggest that post-encoding memory reinstatement is akin to the rapid formation of unique and meaningful episodes that unfold over time.

Semantic Congruence Drives Long-Term Memory and Similarly Affects Neural Retrieval Dynamics in Young and Older Adults.

Learning novel information can be promoted if it is congruent with already stored knowledge. This so-called semantic congruence effect has been broadly studied in healthy young adults with a focus on neural encoding mechanisms. However, the impacts on retrieval, and possible impairments during healthy aging, which is typically associated with changes in declarative long-term memory, remain unclear. To investigate these issues, we used a previously established paradigm in healthy young and older humans with a focus on the neural activity at a final retrieval stage as measured with electroencephalography (EEG). In both age groups, semantic congruence at encoding enhanced subsequent long-term recognition memory of words. Compatible with this observation, semantic congruence led to differences in event-related potentials (ERPs) at retrieval, and this effect was not modulated by age. Specifically, congruence modulated old/new ERPs at a fronto-central (Fz) and left parietal (P3) electrode in a late (400-600 ms) time window, which has previously been associated with recognition memory processes. Importantly, ERPs to old items also correlated with the positive effect of semantic congruence on long-term memory independent of age. Together, our findings suggest that semantic congruence drives subsequent recognition memory across the lifespan through changes in neural retrieval processes.

Functional coupling between CA3 and laterobasal amygdala supports schema dependent memory formation.

The medial temporal lobe drives semantic congruence dependent memory formation. However, the exact roles of hippocampal subfields and surrounding brain regions remain unclear. Here, we used an established paradigm and high-resolution functional magnetic resonance imaging of the medial temporal lobe together with cytoarchitectonic probability estimates in healthy humans. Behaviorally, robust congruence effects emerged in young and older adults, indicating that schema dependent learning is unimpaired during healthy aging. Within the medial temporal lobe, semantic congruence was associated with hemodynamic activity in the subiculum, CA1, CA3 and dentate gyrus, as well as the entorhinal cortex and laterobasal amygdala. Importantly, a subsequent memory analysis showed increased activity for later remembered vs. later forgotten congruent items specifically within CA3, and this subfield showed enhanced functional connectivity to the laterobasal amygdala. As such, our findings extend current models on schema dependent learning by pinpointing the functional properties of subregions within the medial temporal lobe.

Reducing Implicit Cognitive Biases Through the Performing Arts.

The aim of the present research was to test whether involvement in a 14-days training program in the performing arts could reduce implicit biases. We asked healthy participants to complete an Implicit Association Test (IAT) to assess biased attitudes to physical illness in two separate sessions, before and after the training program. Two separate control groups matched by age, gender and educational level completed the two IAT sessions, separated by same number of days, without being involved in the training program. Results showed that participants who were involved in the training program reduced their implicit bias toward illness measured through IAT in the second session. This reduction in IAT measures was not observed in the control samples, despite the two IAT measures being matched in temporal delay with the experimental group. These findings suggest that an interventional program based on the performing arts could be effective in reducing levels of implicit biases among the general population.

Behavioural and neurophysiological signatures in the retrieval of individual memories of recent and remote real-life routine episodic events.

Autobiographical memory (AM) has been largely investigated as the ability to recollect specific events that belong to an individual's past. However, how we retrieve real-life routine episodes and how the retrieval of these episodes changes with the passage of time remain unclear. Here, we asked participants to use a wearable camera that automatically captured pictures to record instances during a week of their routine life and implemented a deep neural network-based algorithm to identify picture sequences that represented episodic events. We then asked each participant to return to the lab to retrieve AMs for single episodes cued by the selected pictures 1 week, 2 weeks and 6-14 months after encoding while scalp electroencephalographic (EEG) activity was recorded. We found that participants were more accurate in recognizing pictured scenes depicting their own past than pictured scenes encoded in the lab, and that memory recollection of personally experienced events rapidly decreased with the passing of time. We also found that the retrieval of real-life picture cues elicited a strong and positive 'ERP old/new effect' over frontal regions and that the magnitude of this ERP effect was similar throughout memory tests over time. However, we observed that recognition memory induced a frontal theta power decrease and that this effect was mostly seen when memories were tested after 1 and 2 weeks but not after 6-14 months from encoding. Altogether, we discuss the implications for neuroscientific accounts of episodic retrieval and the potential benefits of developing individual-based AM exploration strategies at the clinical level.

Theta rhythm supports hippocampus-dependent integrative encoding in schematic/semantic memory networks.

Integrating new information into existing schematic/semantic structures of knowledge is the basis of learning in our everyday life as it enables structured representation of information and goal-directed behaviour in an ever-changing environment. However, how schematic/semantic mnemonic structures aid the integration of novel elements remains poorly understood. Here, we showed that the ability to integrate novel picture information into learned structures of picture associations that overlapped by the same picture scene (i.e., simple network) or by a conceptually related picture scene (i.e., schematic/semantic network) is hippocampus-dependent, as patients with lesions at the medial temporal lobe (including the hippocampus) were impaired in inferring novel relations between pictures within these memory networks. We also found more persistent and widespread scalp EEG theta oscillations (3-5 Hz) while participants integrated novel pictures into schematic/semantic memory networks than into simple networks. On the other hand, greater neural similarity was observed between EEG patterns elicited by novel and related events within simple networks than between novel and related events within schematic/semantic memory networks. These findings have important implications for our understanding of the neural mechanisms that support the development and organization of structures of knowledge.

Neural oscillations and event-related potentials reveal how semantic congruence drives long-term memory in both young and older humans.

Long-term memory can improve when incoming information is congruent with known semantic information. This so-called congruence effect has widely been shown in younger adults, but age-related changes and neural mechanisms remain unclear. Here, congruence improved recognition memory in younger and older adults (i.e. congruence effect), with only weak evidence for age-related decline in one behavioral study. In an EEG study, however, no significant behavioral differences in the congruence effect could be observed between age-groups. In line with this observation, electroencephalography data show that, in both groups, congruence led to widespread differences in Event-Related Potentials (ERPs), starting at around 400 ms after stimulus onset, and theta, alpha and beta oscillations (4-20 Hz). Importantly, these congruence-related ERPs were associated to increases in memory performance for congruent items, in both age groups. Finally, the described ERPs and neural oscillations in the theta-alpha range (5-13 Hz) were less pronounced in the elderly despite a preserved congruence effect. Together, semantic congruence increases long-term memory across the lifespan, and, at the neural level, this could be linked to neural oscillations in the theta, alpha and beta range, as well as ERPs that were previously associated with semantic processing.

Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep.

Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, whether sleep can strengthen deteriorated memories caused by insufficient sleep remains unknown. Here, we showed that sleep restriction in a group of participants caused a reduction in the stability of EEG activity patterns across multiple encoding of the same event during awake, compared with a group of participants that got a full night's sleep. The decrease of neural stability patterns in the sleep-restricted group was associated with higher slow oscillation-spindle coupling during a subsequent night of normal sleep duration, thereby suggesting the instantiation of restorative neural mechanisms adaptively supporting cognition and memory. Importantly, upon awaking, the two groups of participants showed equivalent retrieval accuracy supported by subtle differences in the reinstatement of encoding-related activity: it was longer lasting in sleep-restricted individuals than in controls. In addition, sustained reinstatement over time was associated with increased coupling between spindles and slow oscillations. Taken together, these results suggest that the strength of prior encoding might be an important moderator of memory consolidation during sleep. Supporting this view, spindles nesting in the slow oscillation increased the probability of correct recognition only for weakly encoded memories. Current results demonstrate the benefit that a full night's sleep can induce to impaired memory traces caused by an inadequate amount of sleep.

Event conjunction: How the hippocampus integrates episodic memories across event boundaries.

Our lives are a continuous stream of experience. Our episodic memories on the other hand have a definitive beginning, middle, and end. Theories of event segmentation suggest that salient changes in our environment produce event boundaries which partition the past from the present and, as a result, produce discretized memories. However, event boundaries cannot completely discretize two memories; any shared conceptual link will lead to the rapid integration of these memories. Here, we present a new framework inspired by electrophysiological research that resolves this apparent contradiction. At its heart, the framework proposes that hippocampal theta-gamma coupling maintains a highly abstract model of an ongoing event and serves to encode this model as an episodic memory. When a second but related event begins, this theta-gamma model is rapidly reconstructed within the hippocampus where new details of the second event can be appended to the existing event model. The event conjunction framework is the first electrophysiological explanation of how event memories can be formed at, and integrated across, event boundaries.

Rapid Memory Reactivation at Movie Event Boundaries Promotes Episodic Encoding.

Segmentation of continuous experience into discrete events is driven by rapid fluctuations in encoding stability at context shifts (i.e., event boundaries), yet the mechanisms underlying the online formation of event memories are poorly understood. We investigated the neural per-time point spatial similarity patterns of the scalp electrophysiological (EEG) activity of 30 human participants (male and female) watching a 50 min movie and found that event boundaries triggered the rapid reinstatement of the just-encoded movie event EEG patterns. We also found that the onset of memory reinstatement at boundary onset was accompanied by a left-lateralized anterior negative ERP effect, which likely reflects the detection of a shift in the narrative structure of the movie. A data-driven approach based on Hidden Markov modeling allowed us to detect event boundaries as shifts between stable patterns of brain EEG activity during encoding, and to identify their reactivation during a free recall task. These results provide the first neurophysiological underpinnings for how the memory systems segment a continuous long stream of experience into episodic events.SIGNIFICANCE OF STATEMENT Memory for specific episodic events are the building blocks of our autobiographical memory. However, it is still unclear how the memory systems structure the unfolding experience into discrete event units that can be understood and remembered at the long-term. Here, we show that the detection of context shifts, or event boundaries, during a 50 min movie viewing triggers the rapid memory reactivation of the just-encoded event to promote its successful encoding into long-term memory. By finding that memory reactivation, a neural mechanism critical for episodic memory formation and consolidation, takes place under these ecologically valid experimental circumstances, our results provide valuable insights into how the brain shapes the ongoing experience into episodic memories in the real-life.

Implicit but not explicit extinction to threat-conditioned stimulus prevents spontaneous recovery of threat-potentiated startle responses in humans.

INTRODUCTION: It has long been posited that threat learning operates and forms under an affective and a cognitive learning system that is supported by different brain circuits. A primary drawback in exposure-based therapies is the high rate of relapse that occurs when higher order areas fail to inhibit responses driven by the defensive circuit. It has been shown that implicit exposure of fearful stimuli leads to a long-lasting reduction in avoidance behavior in patients with phobia. Despite the potential benefits of this approach in the treatment of phobias and posttraumatic stress disorder, implicit extinction is still underinvestigated. METHODS: Two groups of healthy participants were threat conditioned. The following day, extinction training was conducted using a stereoscope. One group of participants was explicitly exposed with the threat-conditioned image, while the other group was implicitly exposed using a continuous flash suppression (CFS) technique. On the third day, we tested the spontaneous recovery of defensive responses using explicit presentations of the images. RESULTS: On the third day, we found that only the implicit extinction group showed reduced spontaneous recovery of defensive responses to the threat-conditioned stimulus, measured by threat-potentiated startle responses but not by the electrodermal activity. CONCLUSION: Our results suggest that implicit extinction using CFS might facilitate the modulation of the affective component of fearful memories, attenuating its expression after 24 hr. The limitations of the CFS technique using threatful stimuli urge the development of new strategies to improve implicit presentations and circumvent such limitations. Our study encourages further investigations of implicit extinction as a potential therapeutic target to further advance exposure-based psychotherapies.

Memory: Theta Rhythm Couples Periodic Reactivation during Memory Retrieval.

Memory retrieval involves the reactivation of memory traces distributed throughout the brain. New research suggests that these memory reactivations have an oscillatory nature and that they are coupled to preferential stages of the hippocampal theta cycle.

Gamma phase-synchrony in autobiographical memory: Evidence from magnetoencephalography and severely deficient autobiographical memory.

The subjective sense of recollecting events from one's past is an essential feature of episodic memory, but the neural mechanisms supporting this capacity are poorly understood. We examined the role of large-scale patterns of neural synchrony using whole-head MEG recordings in healthy adults and S.M., who has severely deficient autobiographical memory (SDAM; Palombo et al., 2015), a syndrome in which autobiographical recollection is absent but other functions (including other mnemonic functions), are normal. MEG was conducted while participants listened to prospectively collected recordings documenting unique personal episodes (PE) that normally evoke rich recollection, as well as a condition including general semantic information that is non-specific in place or time (GS; Levine et al., 2004). We predicted that PE (and not GS) would be associated with changes in patterns of large-scale neural synchrony in comparison subjects. We found large-scale neural synchrony, specifically in the gamma frequency ranges (i.e., 27-45Hz), specific to PE and not GS. These synchrony differences between PE and GS were not apparent in S.M. Our findings provide empirical evidence for the supporting role of large-scale gamma neural synchrony underlying autobiographical recollection.

Event Boundaries Trigger Rapid Memory Reinstatement of the Prior Events to Promote Their Representation in Long-Term Memory.

Although everyday experiences unfold continuously over time, shifts in context, or event boundaries, can influence how those events come to be represented in memory [1-4]. Specifically, mnemonic binding across sequential representations is more challenging at context shifts, such that successful temporal associations are more likely to be formed within than across contexts [1, 2, 5-9]. However, in order to preserve a subjective sense of continuity, it is important that the memory system bridge temporally adjacent events, even if they occur in seemingly distinct contexts. Here, we used pattern similarity analysis to scalp electroencephalographic (EEG) recordings during a sequential learning task [2, 3] in humans and showed that the detection of event boundaries triggered a rapid memory reinstatement of the just-encoded sequence episode. Memory reactivation was detected rapidly (∼200-800 ms from the onset of the event boundary) and was specific to context shifts that were preceded by an event sequence with episodic content. Memory reinstatement was not observed during the sequential encoding of events within an episode, indicating that memory reactivation was induced specifically upon context shifts. Finally, the degree of neural similarity between neural responses elicited during sequence encoding and at event boundaries correlated positively with participants' ability to later link across sequences of events, suggesting a critical role in binding temporally adjacent events in long-term memory. Current results shed light onto the neural mechanisms that promote episodic encoding not only for information within the event, but also, importantly, in the ability to link across events to create a memory representation of continuous experience.

Targeted Memory Reactivation during Sleep Adaptively Promotes the Strengthening or Weakening of Overlapping Memories.

System memory consolidation is conceptualized as an active process whereby newly encoded memory representations are strengthened through selective memory reactivation during sleep. However, our learning experience is highly overlapping in content (i.e., shares common elements), and memories of these events are organized in an intricate network of overlapping associated events. It remains to be explored whether and how selective memory reactivation during sleep has an impact on these overlapping memories acquired during awake time. Here, we test in a group of adult women and men the prediction that selective memory reactivation during sleep entails the reactivation of associated events and that this may lead the brain to adaptively regulate whether these associated memories are strengthened or pruned from memory networks on the basis of their relative associative strength with the shared element. Our findings demonstrate the existence of efficient regulatory neural mechanisms governing how complex memory networks are shaped during sleep as a function of their associative memory strength.SIGNIFICANCE STATEMENT Numerous studies have demonstrated that system memory consolidation is an active, selective, and sleep-dependent process in which only subsets of new memories become stabilized through their reactivation. However, the learning experience is highly overlapping in content and thus events are encoded in an intricate network of related memories. It remains to be explored whether and how memory reactivation has an impact on overlapping memories acquired during awake time. Here, we show that sleep memory reactivation promotes strengthening and weakening of overlapping memories based on their associative memory strength. These results suggest the existence of an efficient regulatory neural mechanism that avoids the formation of cluttered memory representation of multiple events and promotes stabilization of complex memory networks.

Amygdala Lesions Reduce Anxiety-like Behavior in a Human Benzodiazepine-Sensitive Approach-Avoidance Conflict Test.

BACKGROUND: Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation. METHODS: In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions. RESULTS: Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report. CONCLUSIONS: Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior.