Stimulating the sleeping brain: Current approaches to modulating memory-related sleep physiology

Background: One of the most audacious proposals throughout the history of psychology was the potential ability to learn while we sleep. The idea penetrated culture via sci-fi movies and inspired the invention of devices that claimed to teach foreign languages, facts, and even quit smoking by simply listening to audiocassettes or other devices during sleep. However, the promises from this endeavor didn't stand up to experimental scrutiny, and the dream was shunned from the scientific community. Despite the historic evidence that the sleeping brain cannot learn new complex information (i.e., words, images, facts), a new wave of current interventions are demonstrating that sleep can be manipulated to strengthen recent memories. New method: Several recent approaches have been developed that play with the sleeping brain in order to modify ongoing memory processing. Here, we provide an overview of the available techniques to non-invasively modulate memory-related sleep physiology, including sensory, vestibular and electrical stimulation, as well as pharmacological approaches. Results: N/A. Comparison with existing methods: N/A. Conclusions: Although the results are encouraging, suggesting that in general the sleeping brain may be optimized for better memory performance, the road to bring these techniques in free-living conditions is paved with unanswered questions and technical challenges that need to be carefully addressed

The benefits of targeted memory reactivation for consolidation in sleep are contingent on memory accuracy and direct cue-memory associations

Objectives: To investigate how the effects of targeted memory reactivation (TMR) are influenced by memory accuracy prior to sleep and the presence or absence of direct cue-memory associations. Methods: 30 participants associated each of 50 pictures with an unrelated word and then with a screen location in two separate tasks. During picture-location training, each picture was also presented with a semantically related sound. The sounds were therefore directly associated with the picture locations but indirectly associated with the words. During a subsequent nap, half of the sounds were replayed in slow wave sleep (SWS) (TMR). The effect of TMR on memory for the picture locations (direct cue-memory associations) and picture-word pairs (indirect cue-memory associations) was then examined. Results: TMR reduced overall memory decay for recall of picture locations. Further analyses revealed a benefit of TMR for picture locations recalled with a low degree of accuracy prior to sleep, but not those recalled with a high degree of accuracy. The benefit of TMR for low accuracy memories was predicted by time spent in SWS. There was no benefit of TMR for memory of the picture-word pairs, irrespective of memory accuracy prior to sleep. Conclusions: TMR provides the greatest benefit to memories recalled with a low degree of accuracy prior to sleep. The memory benefits of TMR may also be contingent on direct cue-memory associations

Shaping memory consolidation via targeted memory reactivation during sleep

Recent studies have shown that the reactivation of specific memories during sleep can be modulated using external stimulation. Specifically, it has been reported that matching a sensory stimulus (e.g., odor or sound cue) with target information (e.g., pairs of words, pictures, and motor sequences) during wakefulness, and then presenting the cue alone during sleep, facilitates memory of the target information. Thus, presenting learned cues while asleep may reactivate related declarative, procedural, and emotional material, and facilitate the neurophysiological processes underpinning memory consolidation in humans. This paradigm, which has been named targeted memory reactivation, has been successfully used to improve visuospatial and verbal memories, strengthen motor skills, modify implicit social biases, and enhance fear extinction. However, these studies also show that results depend on the type of memory investigated, the task employed, the sensory cue used, and the specific sleep stage of stimulation. Here, we present a review of how memory consolidation may be shaped using noninvasive sensory stimulation during sleep

Effects of slow oscillatory transcranial direct current stimulation (so-tDCS) on sleep-dependent memory consolidation

Hintergrund: Es gibt zunehmende Evidenz, dass Schlaf eine aktive Rolle in der Gedächtniskonsolidierung spielt. Insbesondere wird in diesem Zusammenhang die Bedeutung langsamer Oszillationen (< 1 Hz) für die schlafbezogenen Gedächtniskonsolidierungsprozesse diskutiert. In einer wegweisenden Studie, in der eine langsam oszillierende transkranielle Gleichstromstimulation (so-tDCS) appliziert wurde, konnte bei jungen Probanden eine erfolgreiche exogene Manipulation dieser langsamen Oszillationen sowie eine Verbesserung des deklarativen Gedächtnisses beobachtet werden. Spätere Studien, die mit ähnlicher Methodik durchgeführt wurden, zeigten jedoch widersprüchliche Ergebnisse. Die Wirksamkeit dieser neuromodulatorischen Technik wird deshalb in Frage gestellt. Ziel: In dieser Studie wurde untersucht, ob mittels so-tDCS spezifische neurale Oszillationen während des Schlafes moduliert werden können und das deklarative Gedächtnis gesteigert werden kann. Das Ziel war es, die Ergebnisse der Pionierstudie an gesunden jungen Probanden zu replizieren. Dazu wurde ein leicht modifiziertes Stimulationsprotokoll verwendet, welches zuvor an älteren Probanden angewandt wurde. Methoden: In einem doppelblinden, placebo-kontrollierten Laborexperiment mit randomisiertem Crossover-Design wurde der Effekt von bifrontal applizierter anodaler so-tDCS (Frequenz 0,75 Hz) während des Schlafstadium 2 (N2) des Non-REM Schlafes auf die Ergebnisse eines Wortpaar-Assoziationstests und einer Finger-Tapping-Aufgabe an 23 gesunden Probanden (Mittelwert ± Standardabweichung: 23.2 ± 1.9 Jahre; 13 Frauen) überprüft. Stimulationseffekte wurden für Schlafstadien, die Schlafspindeldichte und die EEG-Power analysiert. Weiterhin wurde der Einfluss der so-tDCS auf die deklarative und prozedurale Gedächtniskonsolidierung überprüft. Ergebnisse: Weder auf Verhaltens-, noch auf physiologischer Ebene wurden signifikante Stimulationseffekte beobachtet. Unter beiden Stimulationsbedingungen verbesserte sich die Gedächtnisleistung über Nacht bei der prozeduralen Aufgabe, während sie sich bei der deklarativen Aufgabe verschlechterte. Hatten die Probanden jedoch zusätzliche Lernmöglichkeiten, verringerte dies die Abnahme der deklarativen Gedächtnisleistung. Unabhängig von der Stimulation kam es zu einer Abnahme der schnellen parietalen Spindeldichte von der Baseline (vor Stimulation) zu den stimulationsfreien Intervallen, während bei der langsamen frontalen Spindeldichte kein signifikanter Unterschied auftrat. Schlussfolgerungen: Die vorliegende Studie konnte die Ergebnisse der Pionierstudie nicht reproduzieren. Unsere Ergebnisse stimmen jedoch mit einer früheren Studie überein, die das gleiche Stimulationsprotokoll bei älteren Probanden verwendete. Das Ausmaß der nächtlichen Konsolidierung von deklarativen Gedächtnisinhalten war davon abhängig, ob es eine Möglichkeit zur Wiederholung der Lerninhalte gab. Die Standardisierung des Studienprotokolls und eine Berücksichtigung individueller Variabilität sind essentiell für so-tDCS Studien.Background: There is growing evidence that sleep plays an active role in memory consolidation. Specially, there are indications that slow oscillations (< 1 Hz) might be involved in sleep-dependent memory consolidation processes. Employing slow oscillatory transcranial direct current stimulation (so-tDCS) during slow-wave sleep, a pioneer study reported a successful exogenous manipulation of slow oscillations accompanied by an enhancement of declarative memory in young participants. However, subsequent studies using similar methodologies yielded contradictory results questioning the effectiveness of this neuromodulatory technique. Aim: This study attempted to modulate specific neural oscillations during sleep and boost declarative memory using so-tDCS with the aim to replicate the findings of a seminal study in young healthy adults, using a slightly modified stimulation protocol previously implemented in elderly participants. Methods: The effect of anodal so-tDCS applied bifrontally (frequency 0.75 Hz) during non-rapid eye movement (NREM) stage 2 sleep (N2) was assessed on a word-pair task and a sequential finger tapping task in 23 healthy participants (mean ± Sd: 23.2 ± 1.9 years; 13 women) in a double-blind, placebo controlled, counterbalanced, randomized crossover design. Stimulation effects were analyzed on sleep stages, sleep spindle densities, and EEG power, as well as on declarative and procedural memory performances. Results: No significant stimulation effects were observed neither on the behavioral performance nor at the physiological level. Under both stimulation conditions, overnight retention raised in the procedural task and declined in the declarative task. However, when participants had additional learning opportunities, the decline in declarative memory performance diminished. Regardless of stimulation, fast parietal spindle densities decreased from baseline (prior to stimulation) to stimulation-free intervals, while slow frontal spindle density showed no significant changes. Conclusion: The present study failed to replicate the results of the pioneer study in this field. However, our findings are in line with a previous study that used the same stimulation protocol in elderly participants. Overnight retention performances in declarative memory were dependent on re-encoding opportunities. Finally, it should be noted that protocol standardization and variability control are essential in so-tDCS studies

Mechanisms of memory retrieval in slow-wave sleep : memory retrieval in slow-wave sleep

Study Objectives: Memories are strengthened during sleep. The benefits of sleep for memory can be enhanced by re-exposing the sleeping brain to auditory cues; a technique known as targeted memory reactivation (TMR). Prior studies have not assessed the nature of the retrieval mechanisms underpinning TMR: the matching process between auditory stimuli encountered during sleep and previously encoded memories. We carried out two experiments to address this issue. Methods: In Experiment 1, participants associated words with verbal and non-verbal auditory stimuli before an overnight interval in which subsets of these stimuli were replayed in slow-wave sleep. We repeated this paradigm in Experiment 2 with the single difference that the gender of the verbal auditory stimuli was switched between learning and sleep. Results: In Experiment 1, forgetting of cued (vs. non-cued) associations was reduced by TMR with verbal and non-verbal cues to similar extents. In Experiment 2, TMR with identical non-verbal cues reduced forgetting of cued (vs. non-cued) associations, replicating Experiment 1. However, TMR with non-identical verbal cues reduced forgetting of both cued and non-cued associations. Conclusions: These experiments suggest that the memory effects of TMR are influenced by the acoustic overlap between stimuli delivered at training and sleep. Our findings hint at the existence of two processing routes for memory retrieval during sleep. Whereas TMR with acoustically identical cues may reactivate individual associations via simple episodic matching, TMR with non-identical verbal cues may utilise linguistic decoding mechanisms, resulting in widespread reactivation across a broad category of memories

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep

Introduction: Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Aims: Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Methods: Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results: Results showed that the sound stimulation increased both slow wave (p =.002) and sleep spindle activity (p Conclusions: We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future.Peer reviewe

Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children

Background and Aim: The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. Hypothesis: We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. Methods:: 30 children (19 females, 10.7 ± 0.8 years of age; mean ± SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Analyses: Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Results and Conclusions: Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e., the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills

Closed-loop auditory stimulation of sleep slow oscillations: Basic principles and best practices.

Sleep is essential for our physical and mental well-being. During sleep, despite the paucity of overt behavior, our brain remains active and exhibits a wide range of coupled brain oscillations. In particular slow oscillations are characteristic for sleep, however whether they are directly involved in the functions of sleep, or are mere epiphenomena, is not yet fully understood. To disentangle the causality of these relationships, experiments utilizing techniques to detect and manipulate sleep oscillations in real-time are essential. In this review, we first overview the theoretical principles of closed-loop auditory stimulation (CLAS) as a method to study the role of slow oscillations in the functions of sleep. We then describe technical guidelines and best practices to perform CLAS and analyze results from such experiments. We further provide an overview of how CLAS has been used to investigate the causal role of slow oscillations in various sleep functions. We close by discussing important caveats, open questions, and potential topics for future research