Targeted transcranial electrical stimulation during short-wave sleep can boost episodic memory by almost 20 percent

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HRL Laboratories, LLC, researchers have published results showing that targeted transcranial electrical stimulation during slow-wave sleep can improve metamemories of specific episodes by nearly 20% after only one viewing of the episode, compared to controls.

Metamemory describes the sensitivity of whether memories are recalled accurately or not, such as during eyewitness testimony.

Unique patterns of transcranial electrical stimulation can be cued during the sleep phase called slow-wave sleep to boost consolidation of new memories into the brain’s permanent long-term memory.

Known as spatiotemporal amplitude-modulated patterns or STAMPS, these stimulation patterns can be targeted to affect particular memories.

In immersive virtual reality experiments, one-minute episodes were first paired with arbitrary STAMPs once during viewing. With subsequent stimulation during sleep, targeted memories were measurably improved after just one viewing.

Before this study, general belief was that targeting individual naturalistic memories would require invasive interventions at the single neuron scale in the hippocampus.

“Our results suggest that, unlike relatively localized brain circuits responsible for regulating mood and movement, episodic memories are processed by a much more widespread network of brain areas,” said HRL principal investigator and lead author Praveen Pilly.

“We believe our study will pave the way for next-generation transcranial brain-machine interfaces that can boost learning and memory in healthy humans for real-world tasks, such as language attainment or piloting skills.

Such a non-invasive approach can also potentially benefit a majority of patients with learning and memory deficits at much lower cost and risk than required for implanting intracranial electrode arrays.

It could also be possible to enhance the efficacy of exposure behavioral therapy with immersive virtual reality using STAMP-based tagging and cueing for the treatment of PTSD.”

Unique patterns of transcranial electrical stimulation can be cued during the sleep phase called slow-wave sleep to boost consolidation of new memories into the brain’s permanent long-term memory.


During sleep, the brain reprocesses and reorganizes prior learning in a memory consolidation process by which labile information becomes stronger, more efficient, and more resistant to interference (for a review see Rasch and Born, 2013).

Non-rapid eye movement (NREM) sleep, which can be divided into three stages, NREM1, NREM2, and NREM3, has been recognized to benefit declarative (explicit) memory consolidation; with specific brain oscillations during NREM sleep playing an important role (Diekelmann and Born, 2010; Rasch and Born, 2013; Staresina et al., 2015).

Critical among these are slow oscillations (SOs) which dominate NREM3 (slow wave) sleep and a significant body of research has investigated their role in learning and memory (Rasch and Born, 2013).

Enhancing SOs during sleep is thought to improve subsequent memory performance by enhancing the strength or coupling between memory-related, nested brain oscillations, including sigma frequency band (12–15 Hz; Cellini and Capuozzo, 2018; Wilckens et al., 2018). Non-invasive transcranial electrical stimulation (tES) has been applied as an intervention to enhance SO activity. For example, Marshall et al. (2006) demonstrated that slow oscillatory transcranial direct current stimulation (tDCS) increased SO activity as well as spindle activity, and in turn enhanced performance on a paired-association task.

A recent meta-analysis of studies involving tDCS, transcranial alternating current stimulation (tACS), and slow oscillatory tDCS during sleep indicates that tES is effective in modulating declarative memory consolidation (Barham et al., 2016).

Previous studies using tES during sleep typically stimulate for several minutes once an individual has been confirmed to be in NREM2 or NREM3 sleep (e.g., Marshall et al., 2006 applied 5 min of continuous 0.75 Hz slow oscillatory tDCS after 4 min of NREM2 sleep).

Recent studies also suggest that the timing of stimulation may be important for optimal enhancement of memory-related brain oscillations. For example, closed-loop sensory stimulation that delivers brief auditory stimulation during the positive peak of the SO results in a beneficial memory effect (Ngo et al., 2013; Santostasi et al., 2015; Ong et al., 2016; Leminen et al., 2017; Papalambros et al., 2017). These studies have shown an increase in SO power and phase-locked spindle activity during the up-state of the SO, and an improvement in subsequent declarative memory performance (for a review see Cellini and Mednick, 2019).

Here, we sought to determine whether short durations of repetitive tDCS delivered throughout NREM2/NREM3 could similarly be used to enhance declarative memory. Such a paradigm offers a couple of potential advantages over the more standard minutes-long paradigm used by Marshall et al. (2006).

First, it offers an opportunity to more regularly and consistently investigate the brain’s acute response to the stimulation. Second, it can potentially reduce the overall dose of stimulation delivered to the individual.

Here, we tested this variation of sleep-based short duration repetitive-tES (SDR-tES) after learning in a novel, ecologically valid, a task that required participants to learn a series of facts presented in a paradigm similar to classroom learning or studying flash cards.

We find that this intermittent, short-duration tES can replicate the critical effects of tES on memory and sleep. Specifically, when delivered during a nap taken after a declarative memory task it leads to both: an increase in the proportion of time spent in NREM3 sleep, and a concurrent improvement in longer-term (48-h post-test) recall of facts.

Physiologically, we find that this type of stimulation boosts the rate of SOs during non-stimulation intervals. No significant changes were noted in phase-locked sigma activity between stimulation and sham.

Retrospective analysis of electroencephalography (EEG)-measured brain activity immediately preceding stimulation suggests a negative correlation between the strength and coherence of local brain activity and the resulting number of SO following stimulation.


Funding: The research was supported by the Defense Advanced Research Project Agency and the Army Research Office as part of the RAM Replay Program.

Source:
HRL Laboratories

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