Elsevier

Cortex

Volume 133, December 2020, Pages 37-47
Cortex

Registered Report
Investigating the role of phase-synchrony during encoding of episodic memories using electrical stimulation

https://doi.org/10.1016/j.cortex.2020.09.006Get rights and content

Abstract

The multi-sensory nature of episodic memories indicates that communication between a multitude of brain areas is required for their effective creation and recollection. Previous studies have suggested that the effectiveness of memory processes depends on theta synchronization (4 Hz) of sensory areas relevant to the memory. This study aimed to manipulate theta synchronization between different sensory areas in order to further test this hypothesis. We intend to entrain visual cortex with 4 Hz alternating current stimulation (tACS), while simultaneously entraining auditory cortex with 4 Hz amplitude-modulated sounds. By entraining these different sensory areas, which pertain to learned audio–visual memory associations, we expect to find that when theta is synchronized across the different sensory areas, the memory performance would be enhanced compared to when theta is not synchronized across the sensory areas. We found no evidence for such an effect in this study. It is unclear whether this is due to an inability of 4 Hz tACS to entrain the visual cortex reliably, or whether sensory entrainment is not the underlying mechanism required for episodic memory.

Introduction

The creation and retrieval of episodic memories depends on communication between a multitude of areas throughout the brain. After information is first received and processed in sensory areas, it is eventually relayed to the hippocampus, a structure that has been implicated in episodic memory processes (Scoville & Milner, 1957). This communication has been suggested to be mediated by oscillatory firing patterns (Hanslmayr, Staresina, & Bowman, 2016; Hanslmayr, Staudigl, & Fellner, 2012; Parish, Hanslmayr, & Bowman, 2018). A prominent frequency range in the hippocampus is the theta rhythm (4 Hz), which is assumed to be relevant to processes involving episodic memory (Griffiths et al., 2018; Jacobs, 2014; Lega, Jacobs, & Kahana, 2012). Experiments in rodents have shown that certain parts of the theta phase modulate long-term potentiation, which is assumed to be the neural mechanism underlying memory encoding (Hasselmo, 2005).

A recent series of experiments from our lab aimed to show similar effects of theta-phase on memory encoding in humans (Clouter, Shapiro, & Hanslmayr, 2017; Wang, Clouter, Chen, Shapiro, & Hanslmayr, 2018). In the first study, video clips accompanied by an arbitrary sound were presented. The participants were instructed to associate the presented videos with the accompanying sound. The videos and sounds were individually theta modulated. For the auditory stimuli, the volume was modulated. For visual stimuli, the luminance was modulated. The visual and auditory information was presented at different phase delays. The video clips could be presented in phase, or out of phase (phase delays of 90°, 180°, and 270°). We found that memory performance was significantly enhanced for clips where the sounds and videos were in phase compared to the out of phase conditions. In order to control for the possibility that only phase synchrony, independent of theta, drives the memory effect, two non-harmonic frequency bands were introduced as control conditions (1.7 Hz and 10.5 Hz), alongside another stimulation condition with a non-stationary waveform. The memory effect was not observed in any of the control conditions, suggesting that the effect depends on phase synchrony specifically in the theta band. The experiment was replicated in a subsequent study, where we recorded neural activity using electroencephalography (EEG) during the experiment (Wang et al., 2018). In this subsequent study we found that at a single-trial level, strength of entrainment could predict memory performance.

These studies together suggest there is an optimal theta-phase for memory. The underlying assumption is that the flickering stimuli entrain the respective sensory areas within the brain (Rager & Singer, 1998). Based on that assumption we hypothesize that this entrainment ultimately affects how easy the items can be bound and processed in the context of memory. However, given the flickering nature of the stimuli used in these experiments, we cannot exclude the possibility that the observed memory effects are largely driven by inherent properties of our visual system. This mainly relates to findings suggesting that the visual system, but not the auditory system, discretely samples the environment in theta and alpha range frequencies (Landau & Fries, 2012, VanRullen et al., 2014). The implication is that by attempting entrainment with such heavily modulated stimuli, any memory effects might be mediated by purely perceptual effects. If entrainment is indeed the underlying mechanism that produces the observed effects, similar results should be observed when changing the mode of entrainment to a method that modulates the visual system more subtly and is less noticeable to the observer. A method for neural entrainment that has gained prominence in recent years is transcranial alternating current stimulation (tACS). This method is hypothesized to cause neural entrainment by biasing neural populations to fire at certain times, over others, without directly causing any action potentials (Antal & Paulus, 2013; Helfrich, Knepper, et al., 2014). This is unlike the flickering stimuli used in the previous studies, which lead to forced overt neural responses in the visual cortex.

The idea for the current study is to attempt entraining the visual system by using tACS over occipital areas while presenting un-modulated videos in unison with theta modulated auditory stimuli. The expectation is that if the previously discussed results are due to entrainment of the sensory modalities, the same effects should be observed, albeit with a smaller effect size since tACS would produce to a more subtle entrainment than a flickering stimulus.

Section snippets

Participants

In a Bayesian analysis framework it is legitimate to monitor the Bayes factor (BF) during data collection, since the BF is not biased in one direction with increasing sample size (unlike traditional frequentist analysis approaches based on p-values) (Berger & Wolpert, 1988; Biel & Friedrich, 2018; Rouder, Morey, Speckman, & Province, 2012). Therefore, the number of tested participants was determined by monitoring the BF of the behavioral memory effect between conditions (with the following

Main results

As described in Methods, the difference in memory performance between the 0° and 180° phase condition was monitored as the dataset was collected. We found that the BF never reached a value of at least 10 for our experimental, nor alternative, hypotheses. We therefore collected the maximum preregistered number of subjects for this study (N = 120). This BF difference eventually reached a value of BF01 = 7.43 in favor of the null hypothesis which is generally interpreted as moderate evidence that

Discussion

This study was unable to verify the findings of the previously described visual flicker studies (Clouter et al., 2017; Wang et al., 2018) using a different method of entrainment of the visual cortex. There could be multiple reasons for this inability to replicate these findings.

Firstly, it is possible that the results of the previous studies on which this study was based, were not inherent to entrainment effects in the brain but rather, due to the intrinsic properties of the presented stimulus

Preregistration and data/materials availability

The Stage 1 manuscript was approved and formally registered on April 15, 2019, and may be downloaded from https://osf.io/qha3k, along with the comments raised during the reviewing process. All code that has been used to analyze the data, along with all the behavioral data and all notes made in the lab over the course of the experiment are available at https://osf.io/3ydph/. Legal copyright restrictions prevent public archiving of the movie material used for the experiment. These materials will

Credit author statement

Mircea van der Plas: Investigation, Formal Analysis, Writing - Original Draft.

Danying Wang: Investigation, Writing - Review & Editing.

John-Stuart Brittain: Supervision, Writing - Review & Editing.

Simon Hanslmayr: Supervision, Writing - Review & Editing.

Open practices

The study in this article earned Open Materials, Open Data and Preregistered badges for transparent practices. Materials and data for the study are available at https://osf.io/3ydph.

Acknowledgments

This work was supported by a grant from the European Research Council (Consolidator Grant Agreement 647954), and a grant from the Economic and Social Research Council (ES/R010072/1) both awarded to S.H. SH is further supported by the Wolfson Foundation and the Royal Society.

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