Elsevier

NeuroImage

Volume 140, 15 October 2016, Pages 99-109
NeuroImage

Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation

https://doi.org/10.1016/j.neuroimage.2016.03.065Get rights and content

Highlights

  • Systematic characterization of tES artifacts on simultaneously recorded EEG and MEG.

  • tES artifacts are non-linearly modulated by heartbeat and respiration for EEG and MEG.

  • Current artifact rejection methods fail to fully remove tES artifacts.

Abstract

Transcranial electric stimulation (tES) is a promising tool to non-invasively manipulate neuronal activity in the human brain. Several studies have shown behavioral effects of tES, but stimulation artifacts complicate the simultaneous investigation of neural activity with EEG or MEG. Here, we first show for EEG and MEG, that contrary to previous assumptions, artifacts do not simply reflect stimulation currents, but that heartbeat and respiration non-linearly modulate stimulation artifacts. These modulations occur irrespective of the stimulation frequency, i.e. during both transcranial alternating and direct current stimulations (tACS and tDCS). Second, we show that, although at first sight previously employed artifact rejection methods may seem to remove artifacts, data are still contaminated by non-linear stimulation artifacts. Because of their complex nature and dependence on the subjects' physiological state, these artifacts are prone to be mistaken as neural entrainment. In sum, our results uncover non-linear tES artifacts, show that current techniques fail to fully remove them, and pave the way for new artifact rejection methods.

Introduction

Manipulative approaches are much needed in systems neuroscience. Take neuronal oscillations as an example. They are ubiquitous in the brain and have been implicated in various functions (Buzsáki and Draguhn, 2004, Fries, 2005, Jensen and Mazaheri, 2010, Siegel et al., 2012, Singer, 1999, Womelsdorf et al., 2014). However, supporting evidence, especially in humans, remains largely correlative and only few studies have addressed this causally (Helfrich et al., 2014, Marshall et al., 2006, Polanía et al., 2012, Romei et al., 2011, Romei et al., 2010, Voss et al., 2014). One strategy to causally assess potential roles of neural oscillations is to manipulate them and to simultaneously measure the effect on neural activity and behavior. This is technically challenging and well-defined experimental protocols as well as analysis pipelines have not been established yet.

Transcranial electric stimulation (tES) is a non-invasive brain stimulation technique, which provides the possibility to control stimulation strength, frequency and, to some extent, stimulation site (Dmochowski et al., 2011, Kanai et al., 2008, Schutter and Hortensius, 2010, Schwiedrzik, 2009). These features render tES and in particular one of its variants, transcranial alternating current stimulation (tACS), suitable for manipulating specific brain rhythms (Herrmann et al., 2013). During tACS, a sinusoidal electrical current at a specific frequency is applied to the subject through electrodes placed on the scalp. The potential of electrical stimulation to manipulate neuronal oscillations has been shown in animal models (Fröhlich and McCormick, 2010, Ozen et al., 2010). However, in humans, tACS has largely been limited to investigating effects on behavior and on neurophysiological aftereffects (Brittain et al., 2013, Herrmann et al., 2013, Marshall et al., 2011, Marshall et al., 2006, Polanía et al., 2012, Zaehle et al., 2010). A key reason for the limited number of studies directly investigating effects on neural activity during stimulation is the massive electrophysiological artifact induced by the stimulation. These artifacts are particularly problematic when attempting to investigate effects on neuronal activity within the same frequency range as the stimulation frequency (Zaehle et al., 2010).

Recently, different approaches have been proposed to remove tES artifacts from EEG and MEG for studying neuronal activity during stimulation (Helfrich et al., 2014, Neuling et al., 2015, Soekadar et al., 2013, Voss et al., 2014). Based on the assumption of linear stimulation artifacts, these methods follow approaches like template subtraction, component analysis, beamforming or temporal filtering. However, a thorough characterization of stimulation artifacts, which is needed for assessing artifact cleaning procedures, is missing. Here we provide this characterization.

Section snippets

Methods outline

We measured EEG and MEG during several different tES conditions. First, we tested if a pure sinusoidal model can explain tES artifacts. Next, we investigated in the time and frequency domain whether heartbeat and respiration modulate tES artifacts. Finally, we used temporal and spectral features of tES artifacts to track them through different stages of available artifact rejection pipelines. The rationale behind each analysis is explained in the Results section.

Participants and experimental protocol

All experiments were conducted

tACS artifacts in EEG and MEG

We recorded EEG and MEG during 11 Hz tACS, 62 Hz tACS, and sham stimulation in 4 subjects. Stimulation currents were injected through two Ag/AgCl electrodes with 1 mA peak-to-peak strength (Fig. 1a). EEG was recorded through the 72 remaining electrodes of the 10–10 electrode system, along with 272 MEG channels. Throughout the experiment, we also recorded the electrocardiogram (ECG) and respiration of subjects. For both, EEG and MEG, during stimulation, signals showed strong artifacts at tACS

Discussion

Here, we provide, to the best of our knowledge, the first systematic characterization of transcranial electric stimulation artifacts on EEG and MEG. We uncovered so far unknown non-linear stimulation artifacts, which reflect the modulation of stimulation artifacts by heartbeat and respiration.

Conclusion

In sum, we have uncovered and characterized non-linear stimulation artifacts in EEG and MEG during transcranial electric stimulation. These artifacts depend on the subjects' physiological state and are not fully accounted for by current artifact rejection methods. Our work shows how to track these artifacts and paves the way for new artifact rejection approaches.

Funding

This work was supported by the Centre for Integrative Neuroscience (Deutsche Forschungsgemeinschaft, EXC 307).

Notes

All authors designed the research; N.N. performed the experiments and analyzed the data; N.N. and M.S. wrote the manuscript.

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