Non-rapid eye movement (NREM) sleep is thought to support memory consolidation through coordinated interactions of cortical slow oscillations (SOs), thalamo-cortical sleep spindles, and hippocampal ripples. While this hierarchical coupling has been well documented in rodents and invasive human recordings, direct evidence in humans remains scarce because ripples are inaccessible to conventional scalp EEG. Recent work, however, suggests that magnetoencephalography (MEG) may provide non-invasive access to hippocampal signals. We therefore asked whether MEG can reveal ripple-like activity during sleep, as reflected in its embedding within canonical SO–spindle dynamics and its relation to memory processing. First, participants slept for 90 minutes during MEG recording, allowing us to characterize the physiology of ripple-like activity during NREM sleep. Source-level analyses revealed that ripple-like events peaked in medial temporal regions. These events were systematically embedded within the canonical SO–spindle framework: ripple occurrence increased during spindle peaks and SO up-states, and convergent analyses demonstrated temporal coupling between ripple-like events, spindles, and SOs. In a targeted memory reactivation (TMR) condition, participants learned word–image associations before sleep, and half of the word cues were re-presented during NREM sleep to trigger memory reactivation. TMR improved memory performance and elicited stronger spindle responses for subsequently remembered than non-remembered cues. Critically, ripple-like events in the medial temporal lobe preferentially occurred during these spindles, linking ripple dynamics to behaviorally relevant memory processing. Together, these findings suggest that MEG may capture physiologically meaningful ripple-like dynamics during NREM sleep, providing a non-invasive window into hippocampo-cortical coordination in humans.

Sleep-dependent memory consolidation has been linked to sleep spindles and relies on reactivation. Yet, we know little about the brain-wide distribution of learning-related reactivation. I will present a simultaneous EEG-fMRI sleep study in which participants were asked to encode a set of hierarchically nested sequences of visual images before and after a period of sleep. Behavioral results show overnight memory improvements that exceed memory changes observed in a no-sleep control group. Further analyses showed ordinal position dependent reaction time and accuracy patterns during retrieval that suggest participants engage in sequential retrieval strategies. EEG analyses could successfully remove MRI related artifacts and detect sleep spindles at rates comparable to previous literature. EEG informed fMRI analyses investigate learning-related reactivation and its cortical distribution.

Recent research in rodent models has revealed arousal levels are not simply decreasing during sleep but show fluctuations that are important for maintaining proper sleep physiology and memory consolidation. In humans, tracking arousal level fluctuations has been methodologically challenging. Here we show recent results of video-based recordings of pupil size, an established indicator of arousal levels, and eye position and speed during human overnight sleep. We show that pupil size dynamics and eye movements are distinct across sleep stages and change as a function of important sleep events across different temporal scales. In particular, pupil size was found to be inversely related to the occurrence of sleep spindle clusters, a marker of sleep resilience. Additionally, we found that not only pupil size but also eye movements increased in speed following K-complexes, a sleep microstructural event that hallmarks changes in arousal levels. Taken together, video-based recordings of pupil size dynamics and eye movements provide valuable insights into the interplay between arousal levels and sleep physiology.

The vagus nerve serves as a critical link between the peripheral and central nervous systems. Within the brain, vagal afferents project to noradrenergic pathways known to contribute to memory formation. Targeted vagus nerve activation has been shown to enhance memory consolidation during wakefulness, yet its potential to modulate memory processes during sleep remains largely unexplored. Sleep offers a promising context for such modulation: during non-rapid eye movement sleep, slow oscillations (SOs) provide a neurophysiological scaffold for systems memory consolidation. We hypothesized that brief, precisely timed vagus nerve activation during SOs modulates neuroplasticity and thereby influences sleep-dependent memory consolidation. To test this, we employed phasic (0.5 s) transcutaneous vagus nerve stimulation (tVNS) time-locked to the down-to-up-state transition and the up-state of SOs. Combining polysomnography with peripheral measures, including heart rate, respiration, and gastric rhythms, allowed us to examine autonomic–central nervous system interactions locked to the stimulation. Memory performance was assessed before and after sleep to link behavioral outcomes with neurophysiological dynamics. This study aims to advance our understanding of how vagal activity interacts with sleep oscillations to support memory, while also opening potential avenues for therapeutic interventions that leverage both central and peripheral mechanisms.

Memory consolidation during sleep is thought to rely on the reactivation of neocortical memory traces, mediated by the cross-frequency coupling of slow oscillations, spindles, and ripples. Thalamocortical sleep spindles (10-15 Hz, 0.5-2 s) are hypothesised to play a key role, providing temporal windows of plasticity facilitating the hippocampo-neocortical dialogue. However, causal evidence for their role in human memory consolidation is limited, and underlying neurobiological mechanisms remain to be explored.

To non-invasively characterise and probe the functional role of spindles in human motor memory consolidation, we applied EEG-triggered transcranial magnetic stimulation (TMS) to the motor cortex time-locked to sleep spindles detected in real-time.

Using spindle-phase-triggered single- and paired-pulse TMS we quantified how corticospinal excitability and short-interval intracortical inhibition (SICI) are modulated by the presence, phase and nesting of spindles in slow oscillations. We replicated a strong suppression of corticospinal excitability from wakefulness to sleep, and a pulsed inhibition of excitability driven by the spindle falling flank. Surprisingly, SICI was not significantly modulated by spindle-phase, suggesting short-latency GABA-A receptor-mediated inhibition may not account for the excitability changes.

In a second study we applied disruptive jittered rTMS-bursts to sleep spindles during nocturnal naps aiming to interfere with the reactivation of motor memories. Behavioural performance on motor sequence learning and word-pair association tasks as well as electrophysiological effects were compared within-subjects (n=20) across spindle-targeted, spindle-free, and sham stimulation nights.

Together, these studies establish real-time EEG-triggered TMS as a unique method to characterise and causally probe the role of sleep spindles in human memory consolidation.