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.

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience.

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula [aI] and anterior prefrontal cortex [aPFC]) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

The Hippocampal Film Editor: Sensitivity and Specificity to Event Boundaries in Continuous Experience.

The function of the human hippocampus is normally investigated by experimental manipulation of discrete events. Less is known about what triggers hippocampal activity during more naturalistic, continuous experience. We hypothesized that the hippocampus would be sensitive to the occurrence of event boundaries, that is, moments in time identified by observers as a transition between events. To address this, we analyzed functional MRI data from two groups: one (n = 253, 131 female) who viewed an 8.5 min film and another (n = 15, 6 female) who viewed a 120 min film. We observed a strong hippocampal response at boundaries defined by independent observers, which was modulated by boundary salience (the number of observers that identified each boundary). In the longer film, there were sufficient boundaries to show that this modulation remained after covarying out a large number of perceptual factors. This hypothesis-driven approach was complemented by a data-driven approach, in which we identified hippocampal events as moments in time with the strongest hippocampal activity. The correspondence between these hippocampal events and event boundaries was highly significant, revealing that the hippocampal response is not only sensitive, but also specific to event boundaries. We conclude that event boundaries play a key role in shaping hippocampal activity during encoding of naturalistic events.SIGNIFICANCE STATEMENT Recent years have seen the field of human neuroscience research transitioning from experiments with simple stimuli to the study of more complex and naturalistic experience. Nonetheless, our understanding of the function of many brain regions, such as the hippocampus, is based primarily on the study of brief, discrete events. As a result, we know little of what triggers hippocampal activity in real-life settings when we are exposed to a continuous stream of information. When does the hippocampus "decide" to respond during the encoding of naturalistic experience? We reveal here that hippocampal activity measured by fMRI during film watching is both sensitive and specific to event boundaries, identifying a potential mechanism whereby event boundaries shape experience by modulation of hippocampal activity.

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures.

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose.

Shifting gears in hippocampus: temporal dissociation between familiarity and novelty signatures in a single event.

The hippocampus is known to be involved in encoding and retrieval of episodes. However, real-life experiences are expected to involve both encoding and retrieval, and it is unclear how the human hippocampus subserves both functions in the course of a single event. We presented participants with brief movie clips multiple times and examined the effect of familiarity on the hippocampal response at event onset versus event offset. Increased familiarity resulted in a decreased offset response, indicating that the offset response is a novelty-related signature. The magnitude of this offset response was correlated, across hippocampal voxels, with an independent measure of successful encoding, based on nonrepeated clips. This suggests that the attenuated offset response to familiar clips reflects reduced encoding. In addition, the posterior hippocampus exhibited an increased onset response to familiar events, switching from an online familiarity signal to an offline novelty signal during a single event. Moreover, participants with stronger memory exhibited increased reactivation of online activity during familiar events, in line with a retrieval signature. Our results reveal a spatiotemporal dissociation between novelty/encoding and familiarity/retrieval signatures, assumed to reflect different computational modes, in response to the same stimulus.

Constructing realistic engrams: poststimulus activity of hippocampus and dorsal striatum predicts subsequent episodic memory.

Encoding of real-life episodic memory commonly involves integration of information as the episode unfolds. Offline processing immediately following event offset is expected to play a role in encoding the episode into memory. In this study, we examined whether distinct human brain activity time-locked to the offset of short narrative audiovisual episodes could predict subsequent memory for the gist of the episodes. We found that a set of brain regions, most prominently the bilateral hippocampus and the bilateral caudate nucleus, exhibit memory-predictive activity time-locked to the stimulus offset. We propose that offline activity in these regions reflects registration to memory of integrated episodes.

Loss of reliable temporal structure in event-related averaging of naturalistic stimuli.

To separate neural signals from noise, brain responses measured in neuroimaging are routinely averaged across space and time. However, such procedures may obscure some properties of neural activity. Recently, multi-voxel pattern analysis methods have demonstrated that patterns of activity across voxels contain valuable information that is concealed by spatial averaging. Here we show that temporal patterns of neural activity contain information that can discriminate different stimuli, even within brain regions that show no net activation to that stimulus class. Furthermore, we find that in many brain regions, responses to natural stimuli are highly context dependent. In such cases, prototypical event-related responses do not even exist for individual stimuli, so that averaging responses to the same stimulus within different contexts may worsen the effective signal-to-noise. As a result, analysis of the temporal structures of single events can reveal aspects of neural dynamics which cannot be detected using standard event-related averaging methods.

The limited reach of surprise: Evidence against effects of surprise on memory for preceding elements of an event.

When reflecting on the past, some of our strongest memories are for experiences that took us by surprise. Extensive research has backed this intuition that we are more likely to remember surprising moments than mundane ones. But what about the moments leading up to the surprise? Are we more likely to remember those as well? While surprise is a well-established modulator of memory, it is unknown whether memory for the entire event will be enhanced, or only for the surprising occurrence itself. We developed a novel paradigm utilising stop-motion films, depicting of a sequence of narrative events, in which specific occurrences could be replaced with surprising ones, while keeping the rest of the film unaltered. Using this design, we tested whether surprise exerts retroactive effects on memory, and specifically whether any potential effect would be confined to elements in the same event as the surprising occurrence. In a large cohort of participants (n = 340), we found strong evidence that surprise did not retroactively modulate memory, neither when participants were tested immediately after study nor when they were tested 24 hours later. We suggest two possible accounts for these findings: (1) that the components of an event are encoded as independent episodic elements (not as a cohesive unit), or (2) that surprise segments experience, sectioning off the preceding elements as a separate event.

Knowledge acquisition is governed by striatal prediction errors.

Discrepancies between expectations and outcomes, or prediction errors, are central to trial-and-error learning based on reward and punishment, and their neurobiological basis is well characterized. It is not known, however, whether the same principles apply to declarative memory systems, such as those supporting semantic learning. Here, we demonstrate with fMRI that the brain parametrically encodes the degree to which new factual information violates expectations based on prior knowledge and beliefs-most prominently in the ventral striatum, and cortical regions supporting declarative memory encoding. These semantic prediction errors determine the extent to which information is incorporated into long-term memory, such that learning is superior when incoming information counters strong incorrect recollections, thereby eliciting large prediction errors. Paradoxically, by the same account, strong accurate recollections are more amenable to being supplanted by misinformation, engendering false memories. These findings highlight a commonality in brain mechanisms and computational rules that govern declarative and nondeclarative learning, traditionally deemed dissociable.

Memory Retrieval in Mice and Men.

Retrieval, the use of learned information, was until recently mostly terra incognita in the neurobiology of memory, owing to shortage of research methods with the spatiotemporal resolution required to identify and dissect fast reactivation or reconstruction of complex memories in the mammalian brain. The development of novel paradigms, model systems, and new tools in molecular genetics, electrophysiology, optogenetics, in situ microscopy, and functional imaging, have contributed markedly in recent years to our ability to investigate brain mechanisms of retrieval. We review selected developments in the study of explicit retrieval in the rodent and human brain. The picture that emerges is that retrieval involves coordinated fast interplay of sparse and distributed corticohippocampal and neocortical networks that may permit permutational binding of representational elements to yield specific representations. These representations are driven largely by the activity patterns shaped during encoding, but are malleable, subject to the influence of time and interaction of the existing memory with novel information.

Peri-encoding predictors of memory encoding and consolidation.

We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones.

Hippocampal immediate poststimulus activity in the encoding of consecutive naturalistic episodes.

In the encoding of narrative episodes, the hippocampus exhibits memory-predictive activity time-locked to stimulus offset. In real life, however, events usually occur in succession, raising the question of how the immediate offline processing of one event is affected by presentation of another. To address this issue, participants were presented with brief narrative movie clips in a functional magnetic resonance imaging scanner. Each clip was immediately followed by an additional, unrelated, clip; by a visually scrambled clip with background auditory noises; or by a fixation cross. Memory for the gist of the clips was tested outside the scanner in a cued-recall test 20 min after termination of the study session. The hippocampus responded at the offset of each clip, even when a second clip was presented in immediate succession, suggesting that the hippocampus processes each brief clip as a discrete event. Presentation of a second narrative clip, and to a lesser degree of a scrambled clip, retroactively interfered with memory for the first clip. In parallel, the offline response of the posterior hippocampus to the first movie was reduced. In the anterior hippocampus, presentation of a second clip did not reduce the overall offline response but significantly reduced the difference in activity between remembered and forgotten clips. These findings are in line with the proposition that immediate offline hippocampal activity reflects registration of episodes to memory and suggest a potential brain correlate of retroactive interference.