Thomas Schreiner

Sleep-dependent memory consolidation relies on the precise coordination of slow oscillations (SOs) and spindles. Respiration has recently emerged as a potential pacemaker of this coordination, but whether it thereby shapes memory processes during sleep remains unknown. Here, we used closed-loop targeted memory reactivation (TMR) in humans (N = 25) to target auditory cues to either each participant's SO-spindle-favored respiratory phase (preferred-phase cueing) or the opposite phase (antiphase cueing). Preferred-phase cueing enhanced associative memory relative to antiphase cueing and promoted more precise spindle alignment to SO up-states. Respiratory phase also shaped the timing of reactivation: preferred-phase cues aligned category-specific reactivation with the ensuing SO up-state, whereas antiphase cues delayed reactivation to later SO-spindle complexes occurring at a similar respiratory phase. These findings identify breathing as an endogenous timing signal that organizes the SO-spindle windows in which memory reactivation unfolds, thereby structuring sleep-dependent consolidation.

Hippocampal ripples are considered a key mechanism of sleep-dependent memory consolidation. In humans, however, their direct investigation has relied on invasive recordings from patients with epilepsy, because EEG provides limited access to fast activity from deep medial temporal structures. Here, we tested whether source-resolved magnetoencephalography can reveal physiologically meaningful ripple-like activity during NREM sleep in healthy humans. These events showed hallmarks expected of sleep ripples: they were most prominent in medial temporal regions and embedded within slow oscillation (SO)–spindle dynamics, occurring preferentially during SO up-states and spindle centers. To test mnemonic relevance, we combined sleep MEG with targeted memory reactivation, in which learning cues were replayed during sleep. TMR improved memory performance, and later remembered cues preferentially recruited medial temporal ripple-like events alongside cortical spindles. Ripple-like events also coincided with enhanced item-specific reactivation during successful TMR. Together, these findings establish MEG as a non-invasive window onto hippocampo-cortical memory dynamics during sleep.

Natural states of consciousness are thought to be regulated by deep brain structures such as the thalamus. However, very little is known about the underlying electrophysiology in humans. Here, using a rare opportunity to directly record from the human thalamus, we identify a hitherto-unreported brain-state-specific oscillation of approximately 19-45 Hz. This oscillation is present only during rapid eye movement (REM) sleep and wakefulness, while being absent during non-REM sleep. The 19-45 Hz oscillation further distinguishes REM sleep microstates, co-occurring with bursts of eye movements, and is specific to the central thalamus, a structure implicated in causing global brain state transitions. The discovery of a distinct oscillatory signature in the central thalamus that distinguishes conscious states opens up avenues to further investigate thalamic contributions to states of consciousness in humans and potentially to refine interventions to treat disorders of consciousness.

Sleep is essentially contributing to human health and well-being through multiple biological functions, including restoration and biosynthesis, brain clearance, energy metabolism, immunological and endocrine processing, synaptic plasticity, memory consolidation, and regulation of cognitive and emotional processes. Sleep disturbances are highly prevalent and are both a symptom and a contributing risk factor for psychiatric, neurological, and somatic disorders. Given the limitations of pharmacological interventions, noninvasive neuromodulation techniques ranging from noninvasive transcranial [transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), temporal interference stimulation (tTIS), and transcranial ultrasound stimulation (TUS)] to peripheral sensory (auditory, olfactory, visual, tactile, vestibular) and electrical nerve (galvanic vestibular, transcutaneous vagus nerve, and median nerve) stimulation have gained increasing attention as potential tools to modulate sleep physiology. These techniques offer promising avenues for both therapeutic applications and fundamental research into sleep-dependent neuroplasticity, interregional communication, and oscillatory activity. However, sleep is not a uniform state but a highly complex and dynamic phenomenon, with intricate macrostructural [e.g., non-rapid eye movement (NREM)-rapid eye movement (REM) sleep balance, sleep efficiency] and microstructural (e.g., hierarchically nested slow waves and spindles) characteristics that contribute to a variety of functions. This complexity necessitates precise targeting strategies, often employing real-time brain state-dependent stimulation, to modulate specific sleep-related processes effectively. In this review, we summarize the functions of sleep and the available noninvasive tools for its modulation, addressing key methodological challenges and providing recommendations for best practices in sleep neuromodulation.

Respiration has been shown to impact memory retrieval, yet the neural dynamics underlying this effect remain unclear. Here, we investigated how respiration shapes both behavioral and neural expressions of memory retrieval by reanalyzing an existing dataset where scalp electroencephalography and respiration recordings were acquired while participants ( N = 18, 15 females) performed an episodic memory task. Our results unveil that respiration influences retrieval-related power fluctuations in the α/β band and concomitant memory reactivation. Specifically, we found that both key neural signatures of successful remembering were comodulated during exhalation, with the strength of the interaction between respiration and reactivation processes being associated with memory performance. Together, these findings suggest that respiration may act as a scaffold for episodic memory retrieval in humans by coordinating the neural conditions that support effective remembering.

Respiration has been shown to impact memory retrieval, yet the neural dynamics underlying this effect remain unclear. Here, we investigated how respiration shapes both behavioral and neural expressions of memory retrieval by re-analyzing an existing dataset where scalp electroencephalography and respiration recordings were acquired while participants (N = 18) performed an episodic memory task. Our results unveil that respiration influences retrieval-related power fluctuations in the ⍺/β band and concomitant memory reactivation. Specifically, we found that both key neural signatures of successful remembering were co-modulated during exhalation, with the strength of the interaction between respiration and reactivation processes being associated with memory performance. Together, these findings suggest that respiration may act as a scaffold for episodic memory retrieval in humans by coordinating the neural conditions that support effective remembering.

Every day, we are exposed to an enormity of information. But how does the brain select which experiences to strengthen into long-term memories? Using scalp electroencephalography in human participants, we find evidence that memories are tagged at encoding for selective strengthening across sleep or wakefulness. For memories retained over sleep, this process was driven by 3-8 Hz theta rhythms at learning, with the magnitude of this theta response predicting the coupling of slow oscillations to sleep spindles in later sleep (an established neural correlate of sleep-dependent memory processing). In turn, slow oscillation-spindle coupling was associated with superior memory retention at a post-sleep test. These findings offer new insights into the neural mechanisms through which our brains determine which information is retained for the future.

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.

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.