Elsevier

Brain Stimulation

Volume 12, Issue 6, November–December 2019, Pages 1508-1516
Brain Stimulation

Prestimulus cortical EEG oscillations can predict the excitability of the primary motor cortex

https://doi.org/10.1016/j.brs.2019.06.013Get rights and content

Highlights

  • We studied the relationship between prestimulus EEG oscillations and MEPs.

  • High prestimulus alpha/low-beta (10–15 Hz) power induced high MEP amplitudes.

  • This relationship was weaker in the eyes-closed state or if TMS intensity was low.

  • EEG-triggered TMS suggested the importance of alpha power.

  • The EEG–MEP relationship was modulated in a state-dependent manner.

Abstract

Background

The motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) vary considerably at rest, but the mechanism underlying this amplitude variation is largely unknown. We hypothesized that prestimulus EEG oscillations modulate the subsequent MEPs in a state-dependent manner.

Objective

We studied the relationship between prestimulus alpha/beta oscillations and MEPs during eyes open (EO)/closed (EC) conditions, and then modulated TMS intensity in the EO condition. Furthermore, we developed an EEG-triggered TMS system (“informed open-loop”) to verify our hypothesis.

Methods

TMS was applied to the left motor cortex. We first compared EEG power differences between high- and low-amplitude MEP epochs in the EO and EC conditions when using a high TMS intensity. Next, we evaluated the effects of varying TMS intensities (high vs. low) on the EEG–MEP relationship. Finally, we used EEG-triggered TMS to determine whether prestimulus EEG oscillations predicted MEP amplitudes.

Results

Prestimulus higher-power alpha/low-beta bands produced larger MEPs only in the high-intensity EO condition. A positive relationship between EEG power and MEP amplitude was observed at C3 and left frontal electrodes. This relationship was obscured when using the lower TMS intensity but was observed in the high-intensity condition at the C3 electrode. EEG-triggered TMS demonstrated that higher alpha power predicted higher MEP amplitudes, but beta power at around 20 Hz did not.

Conclusions

A causal relationship between alpha/low-beta oscillations and MEP amplitudes at rest requires high TMS intensity delivered when eyes are open. This association may allow us to develop a new informed open-loop TMS protocol.

Introduction

Motor evoked-potential (MEP) amplitudes reflect the excitability of primary motor cortex (M1) and the spinal cord. MEP and H-reflex amplitudes (a measurement of spinal cord activity) are weakly and positively correlated, with amplitude variability being larger for MEPs [1]. Thus, MEP amplitudes primarily reflect M1 excitability. MEP amplitudes vary considerably, their coefficients of variance are reported to range from 20% to 100% [1,2]. Thus, MEP variability might interfere with the estimation of corticospinal excitability. Indeed, baseline MEP amplitudes have been reported to partially explain response variability in non-invasive brain stimulation (NIBS) [3]. Therefore, a better understanding of the neural substrates that govern MEP-amplitude fluctuation could lead to improved methods for obtaining stable MEP amplitudes and to a more sensitive estimation of NIBS effects.

Electroencephalography (EEG) is widely used to measure cortical activity, and alpha/beta oscillations are generally considered to be linked to several processes, including the inhibition of irrelevant processing, maintenance of movement, and sensorimotor integration during various task conditions [[4], [5], [6]]. In line with this outlook, M1 excitability is enhanced in many motor-task conditions, such as motor execution, observation, and imagery, while at the same time, alpha/beta oscillations are suppressed [[7], [8], [9], [10], [11]]. Additionally, several studies have shown that alpha/beta oscillations are inhibited when MEP amplitudes are large [[12], [13], [14], [15]], although a statistically significant relationship has not always been observed [16,17]. Thus, alpha/beta oscillations are generally considered to be negatively correlated with cortical excitability when doing some action, but this relationship is not conclusive for amplitude fluctuations during resting states. Several studies have used transcranial magnetic stimulation (TMS) to study the EEG-MEP relationship, applying an intensity roughly equal to the resting motor threshold (RMT) [[12], [13], [14], [15], [16]]. This is lower than the intensity ordinarily used to obtain 1-mV MEPs (SI1mV). While weak TMS (∼RMT) over M1 only activates M1, higher intensity TMS also stimulates surrounding areas, such as the premotor area and primary sensory cortex (S1), which might influence MEP amplitudes. Recently, MEP amplitudes measured after stimulating with an intensity that can result in a half-maximum amplitude have been reported to be positively related to EEG alpha oscillations during resting states [18]. Therefore, the EEG–MEP relationship when using a higher TMS intensity such as SI1mV is worth investigating.

Furthermore, eyes-open (EO) and eyes-closed (EC) states not only determine the visual input to the occipital cortex, but also modulate global connectivity [19]. MEPs are usually recorded during the EO state to ensure participant vigilance. However, if the relationship between EEG signals and MEP amplitudes depends on EO/EC at rest, considering these two conditions is important. To date, while a few studies have reported an effect of EO/EC on M1 excitability [[20], [21], [22]], how EO/EC states influence the EEG–MEPs relationship remains unknown.

Based on these findings, our first aim was to determine the relationship between prestimulus EEG alpha/beta band oscillations and MEP amplitude when delivering TMS at an SI1mV intensity, during both EO and EC conditions. In a second experiment, we compared MEP amplitudes produced by high (SI1mV) and low (RMT) TMS intensity in the EO condition. Finally, TMS modulation such as an informed open-loop or closed-loop stimulation has gained recent attention [[23], [24], [25]]. An informed open-loop refers to state-dependent adjustments in stimulus parameters such as time or intensity, while a closed-loop refers to stimulus-parameter adjustment based on participant feedback [25]. these are thought to have the potential to improve NIBS efficacy. Thus, in a third experiment, we developed an EEG-triggered informed open-loop TMS system to verify the findings of the first and second experiments. We also hoped that the informed open-loop TMS setup would help with the design of a new NIBS protocol for neuromodulation.

Section snippets

MEPs

A pair of electrodes were attached to the right first dorsal interosseous muscle (Fig. 1). The electromyographic (EMG) signal was amplified by Neuropack 8 (Nihon Kohden, Tokyo, Japan) with a 10–2000 Hz band-pass filter. The signal was sampled at 10 kHz and stored in a Windows PC for offline analysis by MultiScope PSTH (Medical Try System, Tokyo, Japan).A Magstim 200 (Magstim Co. Ltd., Whitland, UK) transcranial magnetic stimulator that delivered a monophasic pulse using a figure-8 coil (70-mm

Experiment 1: differential effects of EO and EC on the EEG–MEP relationship

Power values ranging from 8 to 30 Hz and from −500 to 0 ms before TMS onset were compared between high-amplitude and low-amplitude MEP epochs. The average numbers of epochs were 94.5 ± 5.8 (mean ± SD) for the EO condition and 96.1 ± 5.3 for the EC condition. Data were separated according to the median MEP values in the EO (756.2 ± 373.4 μV) and EC (702.4 ± 311.6 μV) conditions, which did not significantly differ from each other (p = 0.31, paired t-test). The power was higher for high-amplitude

Discussion

We investigated the relationship between prestimulus EEG power in alpha/low-beta bands and MEP amplitudes while modulating the condition (EO or EC) and TMS intensity (high or low). Analysis revealed that EEG oscillations in the alpha/low-beta power range reflect M1 excitability at rest. Further, an EO state and a TMS intensity of SI1mV were important for estimating the EEG–MEP relationship. The EEG-triggered TMS system confirmed that higher alpha-band power predicted higher MEP amplitudes, and

Conclusions

We found a relationship between alpha/low-beta EEG oscillations and MEP amplitudes at rest, which depended on an EO state and high TMS intensity. Thus, the EEG-MEP relationship is modulated in a state-dependent manner. The obscured relationship during the EC state may be caused by the switch between exteroceptive and interoceptive networks that link sensorimotor oscillations and M1 excitability. Our informed open-loop TMS system also predicted M1 excitability by alpha-band power. Therefore, our

Funding

This study was supported by JSPS KAKENHI [grant numbers JP16K01963 and 15K21731].

Declarations of interest

None.

Acknowledgments

We thank Nia Cason, PhD, and Lesley McCollum, PhD, and Adam Phillips, PhD from Edanz Group (www.edanzediting.com/ac) for editing drafts of this manuscript.

References (50)

  • F.E. Leon-Sarmiento et al.

    Visual deprivation effects on human motor cortex excitability

    Neurosci Lett

    (2005)
  • P.M. Rossini et al.

    Brain excitability and electroencephalographic activation: non-invasive evaluation in healthy humans via transcranial magnetic stimulation

    Brain Res

    (1991)
  • T.O. Bergmann et al.

    Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: current approaches and future perspectives

    Neuroimage

    (2016)
  • J.W. Peirce

    PsychoPy-Psychophysics software in Python

    J Neurosci Methods

    (2007)
  • A. Delorme et al.

    EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis

    J Neurosci Methods

    (2004)
  • B. Hjorth

    An on-line transformation of EEG scalp potentials into orthogonal source derivations

    Electroencephalogr Clin Neurophysiol

    (1975)
  • J.F. Nielsen

    Improvement of amplitude variability of motor evoked potentials in multiple sclerosis patients and in healthy subjects

    Electroencephalogr Clin Neurophysiol

    (1996)
  • E. Maris et al.

    Nonparametric statistical testing of EEG- and MEG-data

    J Neurosci Methods

    (2007)
  • G. Pfurtscheller et al.

    Event-related EEG/MEG synchronization and desynchronization: basic principles

    Clin Neurophysiol

    (1999)
  • P.L. Nunez et al.

    A theoretical and experimental study of high resolution EEG based on surface Laplacians and cortical imaging

    Electroencephalogr Clin Neurophysiol

    (1994)
  • L. Jäncke et al.

    Converging evidence of ERD/ERS and BOLD responses in motor control research

    Prog Brain Res

    (2006)
  • G. Pfurtscheller

    The cortical activation model (CAM)

    Prog Brain Res

    (2006)
  • R. Salmelin et al.

    Spatiotemporal characteristics of sensorimotor neuromagnetic rhythms related to thumb movement

    Neuroscience

    (1994)
  • R. Salmelin et al.

    Functional segregation of movement-related rhythmic activity in the human brain

    Neuroimage

    (1995)
  • C.V. Turco et al.

    Short- and long-latency afferent inhibition; uses, mechanisms and influencing factors

    Brain Stimul

    (2018)
  • Cited by (22)

    • Bihemispheric sensorimotor oscillatory network states determine cortical responses to transcranial magnetic stimulation

      2022, Brain Stimulation
      Citation Excerpt :

      Furthermore, M1 is not functionally segregated but dynamically integrated in extended sensorimotor networks [29,30]. Even ‘eyes closed’ and ‘eyes open’ conditions can affect motor responses to TMS [26]. In an integrative perspective, the spontaneous neural activities generated from the local cortices are organized into hierarchically nested specific global states [10,11,31].

    • Does pericentral mu-rhythm “power” corticomotor excitability? – A matter of EEG perspective

      2021, Brain Stimulation
      Citation Excerpt :

      They found multiple cortical sources of the Mu rhythm in frontoparietal networks but quite consistently reported that its expression peaks in the postcentral somatosensory cortex [34–38]. A predominantly postcentral origin of the Mu-rhythm would also help to explain the contradictory findings of previous work: Studies using the more posterior Laplacian filter [23,25] more often reported significant correlations between MEP amplitude and power than studies that used other ways of mu-extraction, often focusing on the more anterior precentral cortex [14,16,18,19,22]. It is worth mentioning that the sensitivity of the Laplacian surface montage to capture a modulatory effect of mu-power on MEP amplitude cannot be attributed to a generally increased sensitivity for the frequency of interest as the Laplacian montage explained less of the general variance in the frequency band of interest when compared to the source projection.

    • Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space

      2021, Brain Stimulation
      Citation Excerpt :

      The corticospinal responses measured by MEPs elicited by single-pulse TMS targeting the M1 vary between trials [58–61]. Recent studies have shown that this variability is associated with neural oscillation power [62–68], phase [57,69,70], or their interaction [71], although one study failed to replicate these findings [72]. Our study showed that pre-stimulus mu-rhythm oscillatory power was correlated with the modulation of cortical and corticospinal excitability (Fig. 5b).

    • Alertness fluctuations when performing a task modulate cortical evoked responses to transcranial magnetic stimulation

      2020, NeuroImage
      Citation Excerpt :

      Furthermore, a series of studies found that the amplitude or phase of pre-TMS EEG oscillations can predict MEP amplitude, including the alpha (Bergmann et al., 2019; Hussain et al., 2018; Ogata et al., 2019; Sauseng et al., 2009; Schulz et al., 2013; Thies et al., 2018; Zarkowski et al., 2006), beta (Mäki and Ilmoniemi, 2010; Keil et al., 2014; Ogata et al., 2019; Schulz et al., 2013; Zrenner et al., 2018) and gamma (Zarkowski et al., 2006) frequency bands. In most recent MEP studies, a significant association between pre-TMS alpha oscillations and MEP amplitude was linked to the sensorimotor mu-rhythm, which shows spatially local effects confined to one or two pre-TMS cycles of mu (Bergmann et al., 2019; Hussain et al., 2018; Madsen et al., 2019; Ogata et al., 2019; Thies et al., 2018; Zrenner et al., 2018). For instance, a recent study by Ogata et al. (2019) found a significant positive association between pre-TMS alpha and MEP amplitude in an eyes-open condition, but not in an eyes-closed condition.

    View all citing articles on Scopus
    View full text