Targeting targeted memory reactivation: characteristics of cued reactivation in sleep

Targeted memory reactivation (TMR) is a technique in which sensory cues associated with memories during wake are used to trigger memory reactivation during subsequent sleep. The characteristics of such cued reactivation, and the optimal placement of TMR cues, remain to be determined. We built an EEG classification pipeline that discriminated reactivation of right- and left-handed movements and found that cues which fall on the up-going transition of the slow oscillation (SO) are more likely to elicit a classifiable reactivation. We also used a novel machine learning pipeline to predict the likelihood of eliciting a classifiable reactivation after each TMR cue using the presence of spindles and features of SOs. Finally, we found that reactivations occurred either immediately after the cue or one second later. These findings greatly extend our understanding of memory reactivation and pave the way for development of wearable technologies to efficiently enhance memory through cueing in sleep.

Theta activity during encoding interacts with NREM sleep oscillations to predict memory generalization

Relatively little is known regarding the interaction between encoding-related neural activity and sleep-based memory consolidation. One suggestion is that a function of encoding-related theta power may be to 'tag' memories for subsequent processing during sleep. This study aimed to extend previous work on the relationships between sleep spindles, slow oscillation-spindle coupling and task-related theta activity with a combined Deese-Roediger-McDermott (DRM) and nap paradigm. This allowed us to examine the influence of task- and sleep-related oscillatory activity on the recognition of both encoded list words and associative theme words. Thirty-three participants (29 females, mean age = 23.2 years) learned and recognised DRM lists separated by either a 2hr wake or sleep period. Mixed-effects modelling revealed the sleep condition endorsed more associative theme words and fewer list words in comparison to the wake group. Encoding related theta power was also found to influence sleep spindle density, and this interaction was predictive of memory outcomes. The influence of encoding-related theta was specific to sleep spindle density, and did not appear to influence the strength of slow oscillation-spindle coupling as it relates to memory outcomes. The finding of interactions between wakeful and sleep oscillatory-related activity in promoting memory and learning has important implications for theoretical models of sleep-based memory consolidation.

Spindle - slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep

After experiences are encoded, post-encoding reactivations during sleep have been proposed to mediate long-term memory consolidation. Spindle-slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal-cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle- and slow spindle-slow oscillation coupling in the consolidation of spatial memory in humans with a virtual water maze task involving allocentric and egocentric learning strategies. Furthermore, we analyzed how resting-state functional connectivity evolved across learning, consolidation, and retrieval of this task using a data-driven approach. Our results show task-related connectivity changes in the executive control network, the default mode network, and the hippocampal network at post-task rest. The hippocampal network could further be divided into two subnetworks of which only one showed modulation by sleep. Decreased functional connectivity in this subnetwork was associated with higher spindle-slow oscillation coupling power, which was also related to better memory performance at test. Overall, this study contributes to a more holistic understanding of the functional resting-state networks and the mechanisms during sleep associated to spatial memory consolidation.

The Overnight Retention of Novel Metaphors Associates With Slow Oscillation–Spindle Coupling but Not With Respiratory Phase at Encoding

Accumulating evidence emphasizes the relevance of oscillatory synchrony in memory consolidation during sleep. Sleep spindles promote memory retention, especially when occurring in the depolarized upstate of slow oscillation (SO). A less studied topic is the inter-spindle synchrony, i.e. the temporal overlap and phasic coherence between spindles perceived in different electroencephalography channels. In this study, we examined how synchrony between SOs and spindles, as well as between simultaneous spindles, is associated with the retention of novel verbal metaphors. Moreover, we combined the encoding of the metaphors with respiratory phase (inhalation/exhalation) with the aim of modulating the strength of memorized items, as previous studies have shown that inhalation entrains neural activity, thereby benefiting memory in a waking condition. In the current study, 27 young adults underwent a two-night mixed-design study with a 12-h delayed memory task during both sleep and waking conditions. As expected, we found better retention over the delay containing sleep, and this outcome was strongly associated with the timing of SO–spindle coupling. However, no associations were observed regarding inter-spindle synchrony or respiratory phase. These findings contribute to a better understanding of the importance of SO–spindle coupling for memory. In contrast, the observed lack of association with inter-spindle synchrony may emphasize the local nature of spindle-related plasticity.

Cross-frequency slow oscillation-spindle coupling in a biophysically realistic thalamocortical neural mass model

Sleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often time-lock and are implicated in the memory formation. Here, we analyze a neural mass model of the thalamo-cortical loop of which the cortical node can generate slow oscillations (approx. 1 Hz) while its thalamic component can generate sleep spindles of σ-band activity (12-15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic node's potassium leak and anomalous rectifying currents, and for different parameter regimes of the cortical node. The latter are: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced σ-band activity in the cortical node, however, is typically strongest during the UP state, which follows a DOWN state "window of opportunity" for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.

Bedtime Music, Involuntary Musical Imagery, and Sleep

Many people listen to music for hours every day, often near bedtime. We investigated whether music listening affects sleep, focusing on a rarely explored mechanism: involuntary musical imagery (earworms). In Study 1 ( N = 199, mean age = 35.9 years), individuals who frequently listen to music reported persistent nighttime earworms, which were associated with worse sleep quality. In Study 2 ( N = 50, mean age = 21.2 years), we randomly assigned each participant to listen to lyrical or instrumental-only versions of popular songs before bed in a laboratory, discovering that instrumental music increased the incidence of nighttime earworms and worsened polysomnography-measured sleep quality. In both studies, earworms were experienced during awakenings, suggesting that the sleeping brain continues to process musical melodies. Study 3 substantiated this possibility by showing a significant increase in frontal slow oscillation activity, a marker of sleep-dependent memory consolidation. Thus, some types of music can disrupt nighttime sleep by inducing long-lasting earworms that are perpetuated by spontaneous memory-reactivation processes.

Spontaneous slow oscillation - slow spindle features predict induced overnight memory retention

Study Objectives Synchronization of neural activity within local networks and between brain regions is a major contributor to rhythmic field potentials such as the EEG. On the other hand, dynamic changes in microstructure and activity are reflected in the EEG, for instance slow oscillation (SO) slope can reflect synaptic strength. SO-spindle coupling is a measure for neural communication. It was previously associated with memory consolidation, but also shown to reveal strong inter-individual differences. In studies, weak electric current stimulation has modulated brain rhythms and memory retention. Here we investigate whether SO-spindle coupling and SO slope during baseline sleep are associated with (predictive of) stimulation efficacy on retention performance. Methods Twenty-five healthy subjects participated in three experimental sessions. Sleep-associated memory consolidation was measured in two sessions, in one anodal transcranial direct current stimulation oscillating at subjects individual SO frequency (so-tDCS) was applied during nocturnal sleep. The third session was without a learning task (baseline sleep). The dependence on SO-spindle coupling and SO-slope during baseline sleep of so-tDCS efficacy on retention performance were investigated. Results Stimulation efficacy on overnight retention of declarative memories was associated with nesting of slow spindles to SO trough in deep non-rapid eye movement baseline sleep. Steepness and direction of SO slope in baseline sleep were features indicative for stimulation efficacy. Conclusions Findings underscore a functional relevance of activity during the SO up-to-down state transition for memory consolidation and provide support for distinct consolidation mechanisms for types of declarative memories.

044 Slow oscillatory transcranial direct current stimulation enhances cognitive performance during subsequent sleep deprivation

Introduction The EEG slow oscillation of < 1 Hertz frequency has been implicated in various sleep functions, sparking a recent interest in slow oscillation enhancement strategies. In a seminal study, Marshall et al. (2006) demonstrated that 25 minutes of a slow oscillatory form of transcranial direct current stimulation (SO-tDCS) during early nocturnal sleep improved subsequent retention of word pairs learned prior to sleep, consistent with a proposed role for the slow oscillation in sleep-related memory consolidation. Another proposed function of the slow oscillation is synaptic downscaling, hypothesized to constitute the physiological basis for satisfying the homeostatic drive for sleep, per the synaptic homeostasis hypothesis of Tononi and Cirelli. We sought to determine if SO-tDCS could enhance the restorative properties of sleep, by enhancing slow oscillation activity, during a restricted sleep opportunity by assessing performance during a subsequent period of sleep deprivation (SD). Methods Twenty-six healthy volunteers were randomized into two groups. Participants either received electrical stimulation with 50 minutes of SO-tDCS at 0.75Hz, or sham stimulation, during the second hour of a restricted two hour sleep opportunity (11:00PM TO 1:00AM), followed by a 46 hour period of SD and then two recovery nights of sleep. Vigilance was assessed periodically with the Psychomotor Vigilance Test (PVT) during a baseline day, SD, and during the two days following recovery sleep nights. Results A mixed linear regression revealed significant main effects of day, group, and the interaction between group and day on mean reaction time (RT). Posthoc analysis revealed faster RTs following stimulation on day 2 of SD. It was also found that participants in the stimulation group had fewer major lapses (RTs > 500 ms) than those in the sham group over the first three days following stimulation. Conclusion Slow oscillatory transcranial direct current stimulation during a portion of a restricted period of sleep appears to enhance sleep’s restorative properties and improves cognitive performance during subsequent sustained wakefulness. The mechanistic basis for this phenomenon may be increased slow oscillation induced synaptic renormalization. Support (if any) Department of Defense Military Operational Medicine Research Program (MOMRP)

Laminar-specific interhemispheric connectivity mapping with bilateral line-scanning fMRI

ABSTRACTDespite extensive studies detecting blood-oxygen-level-dependent (BOLD) fMRI signals across two hemispheres to present cognitive processes in normal and diseased brains, the role of corpus callosum (CC) to mediate interhemispheric functional connectivity remains controversial. Several studies show maintaining low-frequency fluctuation of resting-state (rs)-fMRI signals in homotopic brain areas of acallosal humans and post-callosotomy animals, raising the question: how can we specify the circuit-specific rs-fMRI signal fluctuation from other sources? To address this question, we have developed a bilateral line-scanning fMRI (BiLS) method to detect bilateral laminar BOLD fMRI signals from symmetric cortical regions with high spatial (100 μm) and temporal (100 ms) resolution in rodents under anesthesia. In addition to ultra-slow oscillation (0.01-0.02 Hz) patterns across all cortical layers, a layer-specific bilateral coherence pattern was observed with a peak at Layer (L)2/3, where callosal projection neurons are primarily located and reciprocal transcallosal projections are received. In particular, the L2/3-specific coherence pattern showed a peak at 0.05 Hz based on the stimulation paradigm, depending on the interhemispheric CC activation. Meanwhile, the L2/3-specific rs-fMRI coherence was peaked at 0.08-0.1Hz which was independent of the varied ultra-slow oscillation patterns (0.01-0.02 Hz) presumably involved with global neuromodulation. This work provides a unique laminar fMRI mapping scheme to characterize the CC-mediated evoked fMRI and frequency-dependent rs-fMRI responses, presenting crucial evidence to distinguish the circuit-specific fMRI signal fluctuations across two hemispheres.Significance statementLaminar fMRI is a promising method to better understand neuronal circuit contribution to functional connectivity (FC) across cortical layers. Here, we developed a bilateral line-scanning fMRI method, allowing the detection of laminar-specific BOLD-fMRI signals from homologous cortical regions in rodents with high spatial and temporal resolution. Laminar coherence patterns of both evoked and rs-fMRI signals revealed that CC-dependent interhemispheric FC is significantly strong at Layer 2/3, where callosal projection neurons are primarily located. The Layer 2/3-specific rs-fMRI coherence is independent of ultra-slow oscillation based on global neuromodulation, distinguishing the circuit-specific rs-fMRI signal fluctuation from different regulatory sources.