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.

Context meta-reinforcement learning via neuromodulation.

Meta-reinforcement learning (meta-RL) algorithms enable agents to adapt quickly to tasks from few samples in dynamic environments. Such a feat is achieved through dynamic representations in an agent's policy network (obtained via reasoning about task context, model parameter updates, or both). However, obtaining rich dynamic representations for fast adaptation beyond simple benchmark problems is challenging due to the burden placed on the policy network to accommodate different policies. This paper addresses the challenge by introducing neuromodulation as a modular component to augment a standard policy network that regulates neuronal activities in order to produce efficient dynamic representations for task adaptation. The proposed extension to the policy network is evaluated across multiple discrete and continuous control environments of increasing complexity. To prove the generality and benefits of the extension in meta-RL, the neuromodulated network was applied to two state-of-the-art meta-RL algorithms (CAVIA and PEARL). The result demonstrates that meta-RL augmented with neuromodulation produces significantly better result and richer dynamic representations in comparison to the baselines.

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.

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.

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.

Thalamic pathways underlying prefrontal cortex-medial temporal lobe oscillatory interactions.

As focus shifts to large-scale network interactions involved in memory, it is becoming increasingly clear that oscillatory dynamics are critically involved. A number of studies have shown a negative correlation between memory retrieval in alpha and beta power, and a positive correlation between retrieval and theta power. In this opinion article, we suggest three thalamic sub-regions responsible for the coordination of oscillatory activity and the facilitation of memory processes. Specifically, the medial dorsal nucleus is related to changes in beta synchrony, the pulvinar is responsible for alpha synchrony, and the anterior thalamus is related to theta synchrony. These pathways may be modulated via frontal control, and changes in oscillations could be used to track the engagement of underlying memory systems.

Identifying objects impairs knowledge of other objects: a relearning explanation for the neural repetition effect.

Different items in long-term knowledge are stored in the neocortex as partially overlapping representations that can be altered slightly with usage. This encoding scheme affords well-documented benefits, but potential costs have not been well explored. Here we use functional magnetic resonance imaging (fMRI), neurocomputational modeling, and electrophysiological measures to show that strengthening some visual object representations not only enhances the subsequent ability to identify those (repeated) objects-an effect long known as repetition priming-but also impairs the ability to identify other (non-repeated) objects-a new effect labeled antipriming. As a result, the non-repeated objects elicit increased neural activity likely for the purpose of reestablishing their previously weakened representations. These results suggest a novel reevaluation of the ubiquitously observed repetition effect on neural activity, and they indicate that maintenance relearning may be a crucial aspect of preserving overlapping neural representations of visual objects in long-term memory.