Spindle-locked ripples mediate memory reactivation during human NREM sleep.

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations.

Electrophysiological signatures of veridical head direction in humans.

Information about heading direction is critical for navigation as it provides the means to orient ourselves in space. However, given that veridical head-direction signals require physical rotation of the head and most human neuroimaging experiments depend upon fixing the head in position, little is known about how the human brain is tuned to such heading signals. Here we adress this by asking 52 healthy participants undergoing simultaneous electroencephalography and motion tracking recordings (split into two experiments) and 10 patients undergoing simultaneous intracranial electroencephalography and motion tracking recordings to complete a series of orientation tasks in which they made physical head rotations to target positions. We then used a series of forward encoding models and linear mixed-effects models to isolate electrophysiological activity that was specifically tuned to heading direction. We identified a robust posterior central signature that predicts changes in veridical head orientation after regressing out confounds including sensory input and muscular activity. Both source localization and intracranial analysis implicated the medial temporal lobe as the origin of this effect. Subsequent analyses disentangled head-direction signatures from signals relating to head rotation and those reflecting location-specific effects. Lastly, when directly comparing head direction and eye-gaze-related tuning, we found that the brain maintains both codes while actively navigating, with stronger tuning to head direction in the medial temporal lobe. Together, these results reveal a taxonomy of population-level head-direction signals within the human brain that is reminiscent of those reported in the single units of rodents.

Respiration modulates sleep oscillations and memory reactivation in humans.

The beneficial effect of sleep on memory consolidation relies on the precise interplay of slow oscillations and spindles. However, whether these rhythms are orchestrated by an underlying pacemaker has remained elusive. Here, we tested the relationship between respiration, which has been shown to impact brain rhythms and cognition during wake, sleep-related oscillations and memory reactivation in humans. We re-analysed an existing dataset, where scalp electroencephalography and respiration were recorded throughout an experiment in which participants (N = 20) acquired associative memories before taking a nap. Our results reveal that respiration modulates the emergence of sleep oscillations. Specifically, slow oscillations, spindles as well as their interplay (i.e., slow-oscillation_spindle complexes) systematically increase towards inhalation peaks. Moreover, the strength of respiration - slow-oscillation_spindle coupling is linked to the extent of memory reactivation (i.e., classifier evidence in favour of the previously learned stimulus category) during slow-oscillation_spindles. Our results identify a clear association between respiration and memory consolidation in humans and highlight the role of brain-body interactions during sleep.

Enabling witnesses to actively explore faces and reinstate study-test pose during a lineup increases discriminability.

Accurate witness identification is a cornerstone of police inquiries and national security investigations. However, witnesses can make errors. We experimentally tested whether an interactive lineup, a recently introduced procedure that enables witnesses to dynamically view and explore faces from different angles, improves the rate at which witnesses identify guilty over innocent suspects compared to procedures traditionally used by law enforcement. Participants encoded 12 target faces, either from the front or in profile view, and then attempted to identify the targets from 12 lineups, half of which were target present and the other half target absent. Participants were randomly assigned to a lineup condition: simultaneous interactive, simultaneous photo, or sequential video. In the front-encoding and profile-encoding conditions, Receiver Operating Characteristics analysis indicated that discriminability was higher in interactive compared to both photo and video lineups, demonstrating the benefit of actively exploring the lineup members' faces. Signal-detection modeling suggested interactive lineups increase discriminability because they afford the witness the opportunity to view more diagnostic features such that the nondiagnostic features play a proportionally lesser role. These findings suggest that eyewitness errors can be reduced using interactive lineups because they create retrieval conditions that enable witnesses to actively explore faces and more effectively sample features.

Cortico-ocular coupling in the service of episodic memory formation.

Encoding of visual information is a necessary requirement for most types of episodic memories. In search for a neural signature of memory formation, amplitude modulation of neural activity has been repeatedly shown to correlate with and suggested to be functionally involved in successful memory encoding. We here report a complementary view on why and how brain activity relates to memory, indicating a functional role of cortico-ocular interactions for episodic memory formation. Recording simultaneous magnetoencephalography and eye tracking in 35 human participants, we demonstrate that gaze variability and amplitude modulations of alpha/beta oscillations (10-20 Hz) in visual cortex covary and predict subsequent memory performance between and within participants. Amplitude variation during pre-stimulus baseline was associated with gaze direction variability, echoing the co-variation observed during scene encoding. We conclude that encoding of visual information engages unison coupling between oculomotor and visual areas in the service of memory formation.

The human thalamus orchestrates neocortical oscillations during NREM sleep.

A hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak -50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak -100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.

Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception.

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.

Saccade-related neural communication in the human medial temporal lobe is modulated by the social relevance of stimuli.

Humans predominantly explore their environment by moving their eyes. To optimally communicate and process visual information, neural activity needs to be coordinated with the execution of eye movements. We investigated the coordination between visual exploration and interareal neural communication by analyzing local field potentials and single neuron activity in patients with epilepsy. We demonstrated that during the free viewing of images, neural communication between the human amygdala and hippocampus is coordinated with the execution of eye movements. The strength and direction of neural communication and hippocampal saccade-related phase alignment were strongest for fixations that landed on human faces. Our results argue that the state of the human medial temporal lobe network is selectively coordinated with motor behavior. Interareal neural communication was facilitated for social stimuli as indexed by the category of the attended information.

Neural activity in the human anterior thalamus during natural vision.

In natural vision humans and other primates explore environment by active sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and in the medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brain's circuitry that is modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using recordings in the human thalamus of three surgical patients during natural vision, we found that saccades and visual stimulus onset both modulate neural activity, but with distinct field potential morphologies. Specifically, we found that fixation-locked field potentials had a component that preceded saccade onset. It was followed by an early negativity around 50 ms after fixation onset which is significantly faster than any response to visual stimulus presentation. The timing of these events suggests that the ANT is predictively modulated before the saccadic eye movement. We also found oscillatory phase concentration, peaking at 3-4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80-180 Hz), both locked to fixation onset supporting the idea that neural oscillations in these nuclei are reorganized to a low excitability state right after fixation onset. These findings show that during real-world natural visual exploration neural dynamics in the human ANT is influenced by visual and oculomotor events, which supports the idea that ANT, apart from their contribution to episodic memory, also play a role in natural vision.

Endogenous memory reactivation during sleep in humans is clocked by slow oscillation-spindle complexes.

Sleep is thought to support memory consolidation via reactivation of prior experiences, with particular electrophysiological sleep signatures (slow oscillations (SOs) and sleep spindles) gating the information flow between relevant brain areas. However, empirical evidence for a role of endogenous memory reactivation (i.e., without experimentally delivered memory cues) for consolidation in humans is lacking. Here, we devised a paradigm in which participants acquired associative memories before taking a nap. Multivariate decoding was then used to capture endogenous memory reactivation during non-rapid eye movement (NREM) sleep in surface EEG recordings. Our results reveal reactivation of learning material during SO-spindle complexes, with the precision of SO-spindle coupling predicting reactivation strength. Critically, reactivation strength (i.e. classifier evidence in favor of the previously studied stimulus category) in turn predicts the level of consolidation across participants. These results elucidate the memory function of sleep in humans and emphasize the importance of SOs and spindles in clocking endogenous consolidation processes.

Alpha/beta power decreases during episodic memory formation predict the magnitude of alpha/beta power decreases during subsequent retrieval.

Episodic memory retrieval is characterised by the vivid reinstatement of information about a personally-experienced event. Growing evidence suggests that this reinstatement is supported by reductions in the spectral power of alpha/beta activity. Given that the amount of information that can be recalled depends on the amount of information that was originally encoded, information-based accounts of alpha/beta activity would suggest that retrieval-related alpha/beta power decreases similarly depend upon decreases in alpha/beta power during encoding. To test this hypothesis, seventeen human participants completed a sequence-learning task while undergoing concurrent MEG recordings. Regression-based analyses were then used to estimate how alpha/beta power decreases during encoding predicted alpha/beta power decreases during retrieval on a trial-by-trial basis. When subjecting these parameter estimates to group-level analysis, we find evidence to suggest that retrieval-related alpha/beta (7-15Hz) power decreases fluctuate as a function of encoding-related alpha/beta power decreases. These results suggest that retrieval-related alpha/beta power decreases are contingent on the decrease in alpha/beta power that arose during encoding. Subsequent analysis uncovered no evidence to suggest that these alpha/beta power decreases reflect stimulus identity, indicating that the contingency between encoding- and retrieval-related alpha/beta power reflects the reinstatement of a neurophysiological operation, rather than neural representation, during episodic memory retrieval.

Electrophysiological signatures of memory reactivation in humans.

The reactivation of neural activity that was present during the encoding of an event is assumed to be essential for human episodic memory retrieval and the consolidation of memories during sleep. Pioneering animal work has already established a crucial role of memory reactivation to prepare and guide behaviour. Research in humans is now delineating the neural processes involved in memory reactivation during both wakefulness and sleep as well as their functional significance. Focusing on the electrophysiological signatures of memory reactivation in humans during both memory retrieval and sleep-related consolidation, this review provides an overview of the state of the art in the field. We outline recent advances, methodological developments and open questions and specifically highlight commonalities and differences in the neuronal signatures of memory reactivation during the states of wakefulness and sleep. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.

Hemispheric Asymmetry of Globus Pallidus Relates to Alpha Modulation in Reward-Related Attentional Tasks.

Whereas subcortical structures such as the basal ganglia have been widely explored in relation to motor control, recent evidence suggests that their mechanisms extend to the domain of attentional switching. We here investigated the subcortical involvement in reward related top-down control of visual alpha-band oscillations (8-13 Hz), which have been consistently linked to mechanisms supporting the allocation of visuospatial attention. Given that items associated with contextual saliency (e.g., monetary reward or loss) attract attention, it is not surprising that the acquired salience of visual items further modulates. The executive networks controlling such reward-dependent modulations of oscillatory brain activity have yet to be fully elucidated. Although such networks have been explored in terms of corticocortical interactions, subcortical regions are likely to be involved. To uncover this, we combined MRI and MEG data from 17 male and 11 female participants, investigating whether derived measures of subcortical structural asymmetries predict interhemispheric modulation of alpha power during a spatial attention task. We show that volumetric hemispheric lateralization of globus pallidus (GP) and thalamus (Th) explains individual hemispheric biases in the ability to modulate posterior alpha power. Importantly, for the GP, this effect became stronger when the value saliency parings in the task increased. Our findings suggest that the GP and Th in humans are part of a subcortical executive control network, differentially involved in modulating posterior alpha activity in the presence of saliency. Further investigation aimed at uncovering the interaction between subcortical and neocortical attentional networks would provide useful insight in future studies.SIGNIFICANCE STATEMENT Whereas the involvement of subcortical regions into higher level cognitive processing, such as attention and reward attribution, has been already indicated in previous studies, little is known about its relationship with the functional oscillatory underpinnings of said processes. In particular, interhemispheric modulation of alpha band (8-13 Hz) oscillations, as recorded with magnetoencephalography, has been previously shown to vary as a function of salience (i.e., monetary reward/loss) in a spatial attention task. We here provide novel insights into the link between subcortical and cortical control of visual attention. Using the same reward-related spatial attention paradigm, we show that the volumetric lateralization of subcortical structures (specifically globus pallidus and thalamus) explains individual biases in the modulation of visual alpha activity.

Reactivation of neural patterns during memory reinstatement supports encoding specificity.

Encoding specificity states that encoding and retrieving items in the same modality benefits memory, compared to encoding and retrieving in different modalities. In neural terms, this can be expressed as memory cues resonating with stored engrams; the more they overlap the better memory performance. We used temporal pattern analysis in MEG in a sensory match/mismatch memory paradigm (i.e., items presented aurally or visually) to track this resonance process. A computational model predicted that reactivation of encoding-related sensory patterns has opposing effects depending on the match or mismatch between memory cue and encoding modality. Behavioral performance was better in the match than the mismatch condition. Neural pattern reinstatement of MEG activity-benefitted memory only in the match condition, but impaired memory in the mismatch condition. These effects were only obtained for aurally but not visually encoded words. The results suggest that reactivation of encoding-related neural patterns underlies encoding specificity.

Theta Phase-Coordinated Memory Reactivation Reoccurs in a Slow-Oscillatory Rhythm during NREM Sleep.

It has been proposed that sleep's contribution to memory consolidation is to reactivate prior encoded information. To elucidate the neural mechanisms carrying reactivation-related mnemonic information, we investigated whether content-specific memory signatures associated with memory reactivation during wakefulness reoccur during subsequent sleep. We show that theta oscillations orchestrate the reactivation of memories during both wakefulness and sleep. Reactivation patterns during sleep autonomously re-emerged at a rate of ∼1 Hz, indicating a coordination by slow oscillatory activity.

Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe Maps Visual Space.

Grid cells are one of the core building blocks of spatial navigation [1]. Single-cell recordings of grid cells in the rodent entorhinal cortex revealed hexagonal coding of the local environment during spatial navigation [1]. Grid-like activity has also been identified in human single-cell recordings during virtual navigation [2]. Human fMRI studies further provide evidence that grid-like signals are also accessible on a macroscopic level [3-7]. Studies in both non-human primates [8] and humans [9, 10] suggest that grid-like coding in the entorhinal cortex generalizes beyond spatial navigation during locomotion, providing evidence for grid-like mapping of visual space during visual exploration-akin to the grid cell positional code in rodents during spatial navigation. However, electrophysiological correlates of the grid code in humans remain unknown. Here, we provide evidence for grid-like, hexadirectional coding of visual space by human high-frequency activity, based on two independent datasets: non-invasive magnetoencephalography (MEG) in healthy subjects and entorhinal intracranial electroencephalography (EEG) recordings in an epileptic patient. Both datasets consistently show a hexadirectional modulation of broadband high-frequency activity (60-120 Hz). Our findings provide first evidence for a grid-like MEG signal, indicating that the human entorhinal cortex codes visual space in a grid-like manner [8-10], and support the view that grid coding generalizes beyond environmental mapping during locomotion [4-6, 11]. Due to their millisecond accuracy, MEG recordings allow linking of grid-like activity to epochs during relevant behavior, thereby opening up the possibility for new MEG-based investigations of grid coding at high temporal resolution.

Across-subjects classification of stimulus modality from human MEG high frequency activity.

Single-trial analyses have the potential to uncover meaningful brain dynamics that are obscured when averaging across trials. However, low signal-to-noise ratio (SNR) can impede the use of single-trial analyses and decoding methods. In this study, we investigate the applicability of a single-trial approach to decode stimulus modality from magnetoencephalographic (MEG) high frequency activity. In order to classify the auditory versus visual presentation of words, we combine beamformer source reconstruction with the random forest classification method. To enable group level inference, the classification is embedded in an across-subjects framework. We show that single-trial gamma SNR allows for good classification performance (accuracy across subjects: 66.44%). This implies that the characteristics of high frequency activity have a high consistency across trials and subjects. The random forest classifier assigned informational value to activity in both auditory and visual cortex with high spatial specificity. Across time, gamma power was most informative during stimulus presentation. Among all frequency bands, the 75 Hz to 95 Hz band was the most informative frequency band in visual as well as in auditory areas. Especially in visual areas, a broad range of gamma frequencies (55 Hz to 125 Hz) contributed to the successful classification. Thus, we demonstrate the feasibility of single-trial approaches for decoding the stimulus modality across subjects from high frequency activity and describe the discriminative gamma activity in time, frequency, and space.

Saccades are phase-locked to alpha oscillations in the occipital and medial temporal lobe during successful memory encoding.

Efficient sampling of visual information requires a coordination of eye movements and ongoing brain oscillations. Using intracranial and magnetoencephalography (MEG) recordings, we show that saccades are locked to the phase of visual alpha oscillations and that this coordination is related to successful mnemonic encoding of visual scenes. Furthermore, parahippocampal and retrosplenial cortex involvement in this coordination reflects effective vision-to-memory mapping, highlighting the importance of neural oscillations for the interaction between visual and memory domains.

Memory-guided attention in the anterior thalamus.

The anterior thalamus is densely connected with both the hippocampus and the prefrontal cortex. It is known to play a role in learning and episodic memory. Given its connectivity profile with the prefrontal cortex, it may also be expected to contribute to executive functions. Recent studies in both rodents and humans add to our understanding of anterior thalamic function, suggesting that it is a key region for allocating attention. We discuss the convergence between studies in rodents and humans, both of which imply that the anterior thalamus may play a key role in memory-guided attention. We suggest that efficient allocation of attention to memory representations requires interaction between the memory-related hippocampal and the attention related fronto-parietal networks. We further propose that the anterior thalamus is a hub that connects and modulates both systems.

No Evidence for Memory Decontextualization across One Night of Sleep.

Sleep after learning strengthens memory consolidation. According to the active system consolidation hypothesis, sleep supports the integration of newly acquired memories into cortical knowledge networks, presumably accompanied by a process of decontextualization of the memory trace (i.e., a gradual loss of memory for the learning context). However, the availability of contextual information generally facilitates memory recall and studies on the interaction of sleep and context on memory retrieval have revealed inconsistent results. Here, we do not find any evidence for a role of sleep in the decontextualization of newly learned declarative memories. In two separate studies, 104 healthy young adults incidentally learned words associated with a context. After a 12 h retention interval filled with either sleep or wakefulness, recall (Experiment 1) or recognition (Experiment 2) was tested with the same or different context. Overall, memory retrieval was significantly improved when the learning context was reinstated, as compared to a different context. However, this context effect of memory was not modulated by sleep vs. wakefulness. These findings argue against a decontextualization of memories, at least across a single night of sleep.