Review
Modulating Human Memory via Entrainment of Brain Oscillations

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Highlights

  • Brain oscillations in various frequency bands have been linked to memory processes.

  • Oscillatory entrainment refers to the modulation of neural oscillations that in the human brain can be achieved via three rhythmic stimulation approaches: sensory stimulation, noninvasive electric/magnetic stimulation, and invasive electrical stimulation.

  • Studies using different techniques of entrainment lend support to the idea that brain oscillations can modulate human memory, and suggest that oscillations are causally relevant for memory processes

In the human brain, oscillations occur during neural processes that are relevant for memory. This has been demonstrated by a plethora of studies relating memory processes to specific oscillatory signatures. Several recent studies have gone beyond such correlative approaches and provided evidence supporting the idea that modulating oscillations via frequency-specific entrainment can alter memory functions. Such causal evidence is important because it allows distinguishing mechanisms directly related to memory from mere epiphenomenal oscillatory signatures of memory. This review provides an overview of stimulation studies using different approaches to entrain brain oscillations for modulating human memory. We argue that these studies demonstrate a causal link between brain oscillations and memory, speaking against an epiphenomenal perspective of brain oscillations.

Section snippets

Brain Oscillations and Memory

Brain oscillations (see Glossary) arise from synchronized interactions between neural populations [1]. Memories are thought to primarily rely on changes in synaptic connectivity, which – among other factors – depend on the level of synchrony between neurons [2]. Therefore, brain oscillations arguably are centrally important for memory processes. Classically, oscillations are divided into different frequency bands including delta, theta, alpha, beta, and gamma oscillations (from slow to fast).

Sensory Entrainment – The Poor Man’s Optogenetics

The idea of inducing oscillatory rhythms via sensory entrainment (Box 2) so as to modulate memory performance is not new [11]. Williams [12] found that the recognition performance of subjects increased when items during encoding followed a ‘flicker’ at 10 Hz (i.e., alpha) compared with a nonflicker condition, as well as compared with slower and faster control frequencies. Similar findings have been obtained using auditory rhythmic stimulation, where memory performance increased after binaural

Noninvasive Electrical (tES) and Electro-Magnetic (rTMS) Entrainment

Additional ways to entrain oscillations noninvasively are transcranial stimulation methods such as transcranial electric stimulation (tES) or repetitive transcranial magnetic stimulation (rTMS; Box 2). In the following we group entrainment studies by the targeted frequencies, starting with slow (delta) oscillations. We also specifically focus on studies which modulate oscillations at the time these processes are assumed to be active (i.e., online stimulation studies), and emphasize studies

Invasive Electrical Entrainment via Deep Brain Stimulation (DBS)

Recent years have seen a prominent increase in the use of oscillatory patterns of invasive stimulation in studies pertaining to memory modulation. Although some studies applied sine waves at 40 Hz (between rhinal cortex and hippocampus [60]), others used low-frequency stimulation (5 Hz [61]) or theta-bursts, namely the application of several stimuli at high frequency that rhythmically alternated (in the theta range) with periods devoid of stimulation 62., 63., 64.. Theta-burst stimulation

Future Directions and Limitations

The studies reviewed above suggest that targeting specific oscillations via invasive and noninvasive entrainment techniques is a promising avenue to modulate memory performance. However, a cautionary note is warranted because there are important methodological limitations that apply to most of the above studies. In particular, the majority of studies reviewed here, including our own, use fairly low sample sizes per experiment (Table 1) which creates the problem of overestimating effect sizes as

Concluding Remarks

This paper set out with the question of whether neural oscillations are of causal relevance for memory or whether they are more of an epiphenomenon. In our view, the studies reviewed here, which use various forms of entraining oscillations, lend support to the former view, namely that brain oscillations do in fact implement specific neural mechanisms subserving the formation, maintenance, consolidation, and retrieval of memories. Although much needs to be done in terms of unraveling how neural

Outstanding Questions

  • What are the neural and computational mechanisms that brain oscillations in different frequency bands implement? How do these mechanisms subserve the formation, maintenance, consolidation, and retrieval of memories?

  • How does neural entrainment affect neural circuit dynamics and structure?

  • How can one increase the efficacy of ‘weak’ stimulation approaches such as tACS?

  • What are the effects of oscillatory DBS on large-scale brain networks, both during stimulation and afterwards?

  • How does oscillatory

Acknowledgements

The authors would like to thank Jürgen Fell and Hong Viet Ngo for helpful comments in preparing this manuscript. S.H. is supported by grants from the European Research Council (grant agreement Nº647954), the Economic and Social Research Council (ESRC grant agreement NºES/R010072/1), and the Wolfson Society and Royal Society. N.A. received funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Projektnummer 316803389 – SFB 1280 as well as via Projektnummer 122679504 –

Glossary

Brain oscillations
the rhythmic activity of a population of neurons within a given frequency band. Brain oscillations can be measured at different spatial scales ranging from below a millimeter in case of local field potentials to about 1 cm for intracranial electroencephalography (iEEG), 1–2 cm for magnetencephalography (MEG), and several centimeters in the case of EEG.
Causality
two variables x and y are causally related if a manipulation of x (e.g., oscillations) causes a change in y (e.g.,

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