Transcranial alternating current stimulation entrains alpha oscillations by preferential phase synchronization of fast-spiking cortical neurons to stimulation waveform

Wei A Huang,Moritz Dannhauer,Iain M Stitt,Thien T Doan,D J Passey,Flavio Fröhlich,Ehsan Negahbani,Anna C Hoover,Susanne Radtke-Schuller,Angel V Peterchev,Sangtae Ahn,Marshall Davey

doi:10.1038/s41467-021-23021-2

Abstract

Computational modeling and human studies suggest that transcranial alternating current stimulation (tACS) modulates alpha oscillations by entrainment. Yet, a direct examination of how tACS interacts with neuronal spiking activity that gives rise to the alpha oscillation in the thalamo-cortical system has been lacking. Here, we demonstrate how tACS entrains endogenous alpha oscillations in head-fixed awake ferrets. We first show that endogenous alpha oscillations in the posterior parietal cortex drive the primary visual cortex and the higher-order visual thalamus. Spike-field coherence is largest for the alpha frequency band, and presumed fast-spiking inhibitory interneurons exhibit strongest coupling to this oscillation. We then apply alpha-tACS that results in a field strength comparable to what is commonly used in humans (<0.5 mV/mm). Both in these ferret experiments and in a computational model of the thalamo-cortical system, tACS entrains alpha oscillations by following the theoretically predicted Arnold tongue. Intriguingly, the fast-spiking inhibitory interneurons exhibit a stronger entrainment response to tACS in both the ferret experiments and the computational model, likely due to their stronger endogenous coupling to the alpha oscillation. Our findings demonstrate the in vivo mechanism of action for the modulation of the alpha oscillation by tACS.

Highlights

Computational modeling and human studies suggest that transcranial alternating current stimulation modulates alpha oscillations by entrainment
We hypothesized that the effect of transcranial alternating current stimulation (tACS) on network dynamics was a result of the synergistic interaction of endogenous network activity and the exogenous electric field delivered by tACS
We demonstrated the acute effect of tACS on neuronal firing coupled to the endogenous alpha oscillations and thereby provide experimental evidence for the previous predictions derived from computational modeling studies about the mechanism of action of entrainment of ongoing oscillations

Summary

Introduction

Computational modeling and human studies suggest that transcranial alternating current stimulation (tACS) modulates alpha oscillations by entrainment. At the single neuron level, tACS polarizes neurons with alternating polarity resulting in a subthreshold resonance where the hyperpolarization-activated cation current plays a key role in the neural response[32,33] Despite these successful demonstrations that weak periodic electric fields interact with neural oscillators, the mechanism of action remains unclear. The major roadblocks for this gap are the technical challenges of simultaneous tACS and EEG recording in human studies, even with some recent attempts to avoid or filter the large electrical artifact of tACS24,35–39 To address this gap in knowledge, we investigated neural entrainment of alpha oscillations by tACS in awake head-fixed ferrets. Our work provides in vivo evidences on how weak electric fields (

Methods

Results

Conclusion