Associations between sleep and episodic memory updating.

Prior research shows that contextual reminders can reactivate hippocampal links to previously consolidated memories, rendering them susceptible to being updated with new information which then is reconsolidated. Studies implicate sleep in the reconsolidation of reactivated memories, but it is unknown what role sleep plays in updating of a previously consolidated trace with new information. We tracked participants' sleep during an episodic reconsolidation paradigm, first with actigraphy (Experiment 1) then with polysomnography (Experiment 2). Our paradigm involved two learning sessions and a retrieval session, each separated by 48 hr. We reminded participants of the first learning experience immediately prior to the second, which led them to update the earlier memory with elements of the later experience. In Experiment 1, less sleep after Session 1 and more sleep after Session 2 are associated with increased updating. In Experiment 2, N2 sleep spindles (SSs) after the reminder and new learning are associated with more updating, but primarily when spindle activity after Session 1 is low. Thus, total sleep time and N2 SSs contribute to sleep-dependent updating of episodic memory. This outcome is consistent with other work connecting SS activity to the integration of novel information into existing knowledge structures, extended here with the study of how variations in sleep over successive nights contribute to this process. We discuss some possible roles of spindles in the decontextualization of hippocampal memory over time. Although much work addresses the role of sleep in the consolidation of new memories, this work uniquely addresses the contribution of sleep to the updating of a previously consolidated trace with new information.

Closed-Loop Slow-Wave tACS Improves Sleep-Dependent Long-Term Memory Generalization by Modulating Endogenous Oscillations.

Benefits in long-term memory retention and generalization have been shown to be related to sleep-dependent processes, which correlate with neural oscillations as measured by changes in electric potential. The specificity and causal role of these oscillations, however, are still poorly understood. Here, we investigated the potential for augmenting endogenous slow-wave (SW) oscillations in humans with closed-loop transcranial alternating current stimulation (tACS) with an aim toward enhancing the consolidation of recent experiences into long-term memory. Sixteen (three female) participants were trained presleep on a target detection task identifying targets hidden in complex visual scenes. During post-training sleep, closed-loop SW detection and stimulation were used to deliver tACS matching the phase and frequency of the dominant oscillation in the range of 0.5-1.2 Hz. Changes in performance were assessed the following day using test images that were identical to the training ("repeated"), and images generated from training scenes but with novel viewpoints ("generalized"). Results showed that active SW tACS during sleep enhanced the postsleep versus presleep target detection accuracy for the generalized images compared with sham nights, while no significant change was found for repeated images. Using a frequency-agnostic clustering approach sensitive to stimulation-induced spectral power changes in scalp EEG, this behavioral enhancement significantly correlated with both a poststimulation increase and a subsequent decrease in measured spectral power within the SW band, which in turn showed increased coupling with spindle amplitude. These results suggest that augmenting endogenous SW oscillations can enhance consolidation by specifically improving generalization over recognition or cued recall.SIGNIFICANCE STATEMENT This human study demonstrates the use of a closed-loop noninvasive brain stimulation method to enhance endogenous neural oscillations during sleep with the effect of improving consolidation of recent experiences into long-term memory. Here we show that transient slow oscillatory transcranial alternating current stimulation (tACS) triggered by endogenous slow oscillations and matching their frequency and phase can increase slow-wave power and coupling with spindles. Further, this increase correlates with overnight improvements in generalization of recent training to facilitate performance in a target detection task. We also provide novel evidence for a tACS-induced refractory period following the tACS-induced increase. Here slow-wave power is temporarily reduced relative to sham stimulation, which nonetheless maintains a positive relationship with behavioral improvements.

Closed-Loop tACS Delivered during Slow-Wave Sleep Reduces Retroactive Interference on a Paired-Associates Learning Task.

Previous studies have found a benefit of closed-loop transcranial alternating current stimulation (CL-tACS) matched to ongoing slow-wave oscillations (SWO) during sleep on memory consolidation for words in a paired associates task (PAT). Here, we examined the effects of CL-tACS in a retroactive interference PAT (ri-PAT) paradigm, where additional stimuli were presented to increase interference and reduce memory performance. Thirty-one participants were tested on a PAT before sleep, and CL-tACS was applied over the right and left DLPFC (F3 and F4) vs. mastoids for five cycles after detection of the onset of each discrete event of SWO during sleep. Participants were awoken the following morning, learned a new PAT list, and then were tested on the original list. There was a significant effect of stimulation condition (p = 0.04297; Cohen's d = 0.768), where verum stimulation resulted in reduced retroactive interference compared with sham and a significant interaction of encoding strength and stimulation condition (p = 0.03591). Planned simple effects testing within levels of encoding revealed a significant effect of stimulation only for low-encoders (p = 0.0066; Cohen's d = 1.075) but not high-encoders. We demonstrate here for the first time that CL-tACS during sleep can enhance the protective benefits on retroactive interference in participants who have lower encoding aptitude.

Brain connectivity alterations during sleep by closed-loop transcranial neurostimulation predict metamemory sensitivity.

Metamemory involves the ability to correctly judge the accuracy of our memories. The retrieval of memories can be improved using transcranial electrical stimulation (tES) during sleep, but evidence for improvements to metamemory sensitivity is limited. Applying tES can enhance sleep-dependent memory consolidation, which along with metamemory requires the coordination of activity across distributed neural systems, suggesting that examining functional connectivity is important for understanding these processes. Nevertheless, little research has examined how functional connectivity modulations relate to overnight changes in metamemory sensitivity. Here, we developed a closed-loop short-duration tES method, time-locked to up-states of ongoing slow-wave oscillations, to cue specific memory replays in humans. We measured electroencephalographic (EEG) coherence changes following stimulation pulses, and characterized network alterations with graph theoretic metrics. Using machine learning techniques, we show that pulsed tES elicited network changes in multiple frequency bands, including increased connectivity in the theta band and increased efficiency in the spindle band. Additionally, stimulation-induced changes in beta-band path length were predictive of overnight changes in metamemory sensitivity. These findings add new insights into the growing literature investigating increases in memory performance through brain stimulation during sleep, and highlight the importance of examining functional connectivity to explain its effects.

Transcranial Current Stimulation During Sleep Facilitates Insight into Temporal Rules, but does not Consolidate Memories of Individual Sequential Experiences.

Slow-wave sleep (SWS) is known to contribute to memory consolidation, likely through the reactivation of previously encoded waking experiences. Contemporary studies demonstrate that when auditory or olfactory stimulation is administered during memory encoding and then reapplied during SWS, memory consolidation can be enhanced, an effect that is believed to rely on targeted memory reactivation (TMR) induced by the sensory stimulation. Here, we show that transcranial current stimulations (tCS) during sleep can also be used to induce TMR, resulting in the facilitation of high-level cognitive processes. Participants were exposed to repeating sequences in a realistic 3D immersive environment while being stimulated with particular tCS patterns. A subset of these tCS patterns was then reapplied during sleep stages N2 and SWS coupled to slow oscillations in a closed-loop manner. We found that in contrast to our initial hypothesis, performance for the sequences corresponding to the reapplied tCS patterns was no better than for other sequences that received stimulations only during wake or not at all. In contrast, we found that the more stimulations participants received overnight, the more likely they were to detect temporal regularities governing the learned sequences the following morning, with tCS-induced beta power modulations during sleep mediating this effect.

One-Shot Tagging During Wake and Cueing During Sleep With Spatiotemporal Patterns of Transcranial Electrical Stimulation Can Boost Long-Term Metamemory of Individual Episodes in Humans.

Targeted memory reactivation (TMR) during slow-wave oscillations (SWOs) in sleep has been demonstrated with sensory cues to achieve about 5-12% improvement in post-nap memory performance on simple laboratory tasks. But prior work has not yet addressed the one-shot aspect of episodic memory acquisition, or dealt with the presence of interference from ambient environmental cues in real-world settings. Further, TMR with sensory cues may not be scalable to the multitude of experiences over one's lifetime. We designed a novel non-invasive non-sensory paradigm that tags one-shot experiences of minute-long naturalistic episodes in immersive virtual reality (VR) with unique spatiotemporal amplitude-modulated patterns (STAMPs) of transcranial electrical stimulation (tES). In particular, we demonstrated that these STAMPs can be re-applied as brief pulses during SWOs in sleep to achieve about 10-20% improvement in the metamemory of targeted episodes compared to the control episodes at 48 hours after initial viewing. We found that STAMPs can not only facilitate but also impair metamemory for the targeted episodes based on an interaction between pre-sleep metamemory and the number of STAMP applications during sleep. Overnight metamemory improvements were mediated by spectral power increases following the offset of STAMPs in the slow-spindle band (8-12 Hz) for left temporal areas in the scalp electroencephalography (EEG) during sleep. These results prescribe an optimal strategy to leverage STAMPs for boosting metamemory and suggest that real-world episodic memories can be modulated in a targeted manner even with coarser, non-invasive spatiotemporal stimulation.

Mental State Assessment and Validation Using Personalized Physiological Biometrics.

Mental state monitoring is a critical component of current and future human-machine interfaces, including semi-autonomous driving and flying, air traffic control, decision aids, training systems, and will soon be integrated into ubiquitous products like cell phones and laptops. Current mental state assessment approaches supply quantitative measures, but their only frame of reference is generic population-level ranges. What is needed are physiological biometrics that are validated in the context of task performance of individuals. Using curated intake experiments, we are able to generate personalized models of three key biometrics as useful indicators of mental state; namely, mental fatigue, stress, and attention. We demonstrate improvements to existing approaches through the introduction of new features. Furthermore, addressing the current limitations in assessing the efficacy of biometrics for individual subjects, we propose and employ a multi-level validation scheme for the biometric models by means of k-fold cross-validation for discrete classification and regression testing for continuous prediction. The paper not only provides a unified pipeline for extracting a comprehensive mental state evaluation from a parsimonious set of sensors (only EEG and ECG), but also demonstrates the use of validation techniques in the absence of empirical data. Furthermore, as an example of the application of these models to novel situations, we evaluate the significance of correlations of personalized biometrics to the dynamic fluctuations of accuracy and reaction time on an unrelated threat detection task using a permutation test. Our results provide a path toward integrating biometrics into augmented human-machine interfaces in a judicious way that can help to maximize task performance.

The Benefits of Closed-Loop Transcranial Alternating Current Stimulation on Subjective Sleep Quality.

BACKGROUND: Poor sleep quality is a common complaint, affecting over one third of people in the United States. While sleep quality is thought to be related to slow-wave sleep (SWS), there has been little investigation to address whether modulating slow-wave oscillations (SWOs) that characterize SWS could impact sleep quality. Here we examined whether closed-loop transcranial alternating current stimulation (CL-tACS) applied during sleep impacts sleep quality and efficiency. METHODS: CL-tACS was used in 21 participants delivered at the same frequency and in phase with endogenous SWOs during sleep. Sleep quality was assessed in the morning following either verum or sham control stimulation during sleep, with order counterbalanced within participants. RESULTS: Higher sleep quality and efficiency were found after verum stimulation nights compared to control. The largest effects on sleep quality were found immediately following an adaptation night in the laboratory for which sleep quality was reduced. CONCLUSIONS: Applying CL-tACS at the same frequency and phase as endogenous SWOs may offer a novel method to improve subjective sleep quality after a night with poor quality sleep. CL-tACS might be helpful for increasing sleep quality and efficiency in otherwise healthy people, and in patients with clinical disorders that involve sleep deficits.

Dose-Dependent Effects of Closed-Loop tACS Delivered During Slow-Wave Oscillations on Memory Consolidation.

Sleep is critically important to consolidate information learned throughout the day. Slow-wave sleep (SWS) serves to consolidate declarative memories, a process previously modulated with open-loop non-invasive electrical stimulation, though not always effectively. These failures to replicate could be explained by the fact that stimulation has only been performed in open-loop, as opposed to closed-loop where phase and frequency of the endogenous slow-wave oscillations (SWOs) are matched for optimal timing. The current study investigated the effects of closed-loop transcranial Alternating Current Stimulation (tACS) targeting SWOs during sleep on memory consolidation. 21 participants took part in a three-night, counterbalanced, randomized, single-blind, within-subjects study, investigating performance changes (correct rate and F1 score) on images in a target detection task over 24 h. During sleep, 1.5 mA closed-loop tACS was delivered in phase over electrodes at F3 and F4 and 180° out of phase over electrodes at bilateral mastoids at the frequency (range 0.5-1.2 Hz) and phase of ongoing SWOs for a duration of 5 cycles in each discrete event throughout the night. Data were analyzed in a repeated measures ANOVA framework, and results show that verum stimulation improved post-sleep performance specifically on generalized versions of images used in training at both morning and afternoon tests compared to sham, suggesting the facilitation of schematization of information, but not of rote, veridical recall. We also found a surprising inverted U-shaped dose effect of sleep tACS, which is interpreted in terms of tACS-induced faciliatory and subsequent refractory dynamics of SWO power in scalp EEG. This is the first study showing a selective modulation of long-term memory generalization using a novel closed-loop tACS approach, which holds great potential for both healthy and neuropsychiatric populations.