Curiosity Satisfaction Increases Event-related Potentials Sensitive to Reward.

Successful learning depends on various factors such as depth of processing, motivation, or curiosity about information. A strong drive to learn something or the expectation of receiving a reward can be crucial to enhance learning. However, the influence of curiosity on the processing of new information and its similarity with reward processing is not well understood. This study examined whether states of curiosity influence specific ERPs associated with reward processing and whether these ERPs are related with later memory benefits. In an initial screening phase, participants indicated their curiosity and confidence in prior knowledge about answers to various trivia questions. In a subsequent study phase, we targeted different time windows related to reward processing during the presentation of trivia answers containing the reward positivity (RewP; 250-350 msec), the P3 (250-500 msec), and the late-positive-potential (LPP; 600-1000 msec). In a following surprise memory test, we found that participants recalled more high- than low-curiosity answers. The RewP, P3, and LPP showed greater positive mean amplitudes for high compared with low curiosity, reflecting increased reward processing. In addition, we found that the RewP and the P3 showed more positive mean amplitudes for later recalled compared with later forgotten answers, but curiosity did not modulate this encoding-related results. These findings support the view that the satisfaction of curiosity resembles reward processing, indicated by ERPs.

Bedside Magnetocardiography with a Scalar Sensor Array.

Decades of research have shown that magnetocardiography (MCG) has the potential to improve cardiac care decisions. However, sensor and system limitations have prevented its widespread adoption in clinical practice. We report an MCG system built around an array of scalar, optically pumped magnetometers (OPMs) that effectively rejects ambient magnetic interference without magnetic shielding. We successfully used this system, in conjunction with custom hardware and noise rejection algorithms, to record magneto-cardiograms and functional magnetic field maps from 30 volunteers in a regular downtown office environment. This demonstrates the technical feasibility of deploying our device architecture at the point-of-care, a key step in making MCG usable in real-world settings.

Contextual Expectations Shape Cortical Reinstatement of Sensory Representations.

When making a turn at a familiar intersection, we know what items and landmarks will come into view. These perceptual expectations, or predictions, come from our knowledge of the context; however, it is unclear how memory and perceptual systems interact to support the prediction and reactivation of sensory details in cortex. To address this, human participants learned the spatial layout of animals positioned in a cross maze. During fMRI, participants of both sexes navigated between animals to reach a target, and in the process saw a predictable sequence of five animal images. Critically, to isolate activity patterns related to item predictions, rather than bottom-up inputs, one-fourth of trials ended early, with a blank screen presented instead. Using multivariate pattern similarity analysis, we reveal that activity patterns in early visual cortex, posterior medial regions, and the posterior hippocampus showed greater similarity when seeing the same item compared with different items. Further, item effects in posterior hippocampus were specific to the sequence context. Critically, activity patterns associated with seeing an item in visual cortex and posterior medial cortex, were also related to activity patterns when an item was expected, but omitted, suggesting sequence predictions were reinstated in these regions. Finally, multivariate connectivity showed that patterns in the posterior hippocampus at one position in the sequence were related to patterns in early visual cortex and posterior medial cortex at a later position. Together, our results support the idea that hippocampal representations facilitate sensory processing by modulating visual cortical activity in anticipation of expected items.SIGNIFICANCE STATEMENT Our visual world is a series of connected events, where we can predict what we might see next based on our recent past. Understanding the neural circuitry and mechanisms of the perceptual and memory systems that support these expectations is fundamental to revealing how we perceive and act in our world. Using brain imaging, we studied what happens when we expect to see specific visual items, and how such expectations relate to top-down memory signals. We find both visual and memory systems reflect item predictions, and moreover, we show that hippocampal activity supports predictions of future expected items. This demonstrates that the hippocampus acts to predict upcoming items, and reinstates such predictions in cortex.

Narratives bridge the divide between distant events in episodic memory.

Many studies suggest that information about past experience, or episodic memory, is divided into discrete units called "events." Yet we can often remember experiences that span multiple events. Events that occur in close succession might simply be linked because of their proximity to one another, but we can also build links between events that occur farther apart in time. Intuitively, some kind of organizing principle should enable temporally distant events to become bridged in memory. We tested the hypothesis that episodic memory exhibits a narrative-level organization, enabling temporally distant events to be better remembered if they form a coherent narrative. Furthermore, we tested whether post-encoding memory consolidation is necessary to integrate temporally distant events. In three experiments, participants learned and subsequently recalled events from fictional stories, in which pairs of temporally distant events involving side characters ("sideplots") either formed one coherent narrative or two unrelated narratives. Across participants, we varied whether recall was assessed immediately after learning, or after a delay: 24 hours, 12 hours between morning and evening ("wake"), or 12 hours between evening and morning ("sleep"). Participants recalled more information about coherent than unrelated narrative events, in most delay conditions, including immediate recall and wake conditions, suggesting that post-encoding consolidation was not necessary to integrate temporally distant events into a larger narrative. Furthermore, post hoc modeling across experiments suggested that narrative coherence facilitated recall over and above any effects of sentence-level semantic similarity. This reliable memory benefit for coherent narrative events supports theoretical accounts which propose that narratives provide a high-level architecture for episodic memory.

Theta oscillations promote temporal sequence learning.

Many theoretical models suggest that neural oscillations play a role in learning or retrieval of temporal sequences, but the extent to which oscillations support sequence representation remains unclear. To address this question, we used scalp electroencephalography (EEG) to examine oscillatory activity over learning of different object sequences. Participants made semantic decisions on each object as they were presented in a continuous stream. For three "Consistent" sequences, the order of the objects was always fixed. Activity during Consistent sequences was compared to "Random" sequences that consisted of the same objects presented in a different order on each repetition. Over the course of learning, participants made faster semantic decisions to objects in Consistent, as compared to objects in Random sequences. Thus, participants were able to use sequence knowledge to predict upcoming items in Consistent sequences. EEG analyses revealed decreased oscillatory power in the theta (4-7 Hz) band at frontal sites following decisions about objects in Consistent sequences, as compared with objects in Random sequences. The theta power difference between Consistent and Random only emerged in the second half of the task, as participants were more effectively able to predict items in Consistent sequences. Moreover, we found increases in parieto-occipital alpha (10-13 Hz) and beta (14-28 Hz) power during the pre-response period for objects in Consistent sequences, relative to objects in Random sequences. Linear mixed effects modeling revealed that single trial theta oscillations were related to reaction time for future objects in a sequence, whereas beta and alpha oscillations were only predictive of reaction time on the current trial. These results indicate that theta and alpha/beta activity preferentially relate to future and current events, respectively. More generally our findings highlight the importance of band-specific neural oscillations in the learning of temporal order information.

Machine Learning Guided AQFEP: A Fast and Efficient Absolute Free Energy Perturbation Solution for Virtual Screening.

Structure-based methods in drug discovery have become an integral part of the modern drug discovery process. The power of virtual screening lies in its ability to rapidly and cost-effectively explore enormous chemical spaces to select promising ligands for further experimental investigation. Relative free energy perturbation (RFEP) and similar methods are the gold standard for binding affinity prediction in drug discovery hit-to-lead and lead optimization phases, but have high computational cost and the requirement of a structural analog with a known activity. Without a reference molecule requirement, absolute FEP (AFEP) has, in theory, better accuracy for hit ID, but in practice, the slow throughput is not compatible with VS, where fast docking and unreliable scoring functions are still the standard. Here, we present an integrated workflow to virtually screen large and diverse chemical libraries efficiently, combining active learning with a physics-based scoring function based on a fast absolute free energy perturbation method. We validated the performance of the approach in the ranking of structurally related ligands, virtual screening hit rate enrichment, and active learning chemical space exploration; disclosing the largest reported collection of free energy simulations to date.

Goal-oriented representations in the human hippocampus during planning and navigation.

Recent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming cognitive maps that capture the abstract structure of physical spaces, tasks, and situations. Navigation involves disambiguating similar contexts, and the planning and execution of a sequence of decisions to reach a goal. Here, we examine hippocampal activity patterns in humans during a goal-directed navigation task to investigate how contextual and goal information are incorporated in the construction and execution of navigational plans. During planning, hippocampal pattern similarity is enhanced across routes that share a context and a goal. During navigation, we observe prospective activation in the hippocampus that reflects the retrieval of pattern information related to a key-decision point. These results suggest that, rather than simply representing overlapping associations or state transitions, hippocampal activity patterns are shaped by context and goals.

The hippocampus constructs narrative memories across distant events.

Life's events are scattered throughout time, yet we often recall different events in the context of an integrated narrative. Prior research suggests that the hippocampus, which supports memory for past events, can support the integration of overlapping associations or separate events in memory. However, the conditions that lead to hippocampus-dependent memory integration are unclear. We used functional brain imaging to test whether the opportunity to form a larger narrative (narrative coherence) drives hippocampal memory integration. During encoding of fictional stories, patterns of hippocampal activity, including activity at boundaries between events, were more similar between distant events that formed one coherent narrative, compared with overlapping events taken from unrelated narratives. One day later, the hippocampus preferentially supported detailed recall of coherent narrative events, through reinstatement of hippocampal activity patterns from encoding. These findings demonstrate a key function of the hippocampus: the integration of events into a narrative structure for memory.