Reproducibility in TMS–EEG studies: A call for data sharing, standard procedures and effective experimental control

Abstract

A recent study by Conde, Tomasevic et al. (2019) [1] puts a spotlight on the subtleties of experimental design and analysis of studies involving TMS-evoked EEG potentials (TEPs), specifically focusing on the challenge of disentangling genuine cortical responses to TMS from those resulting from concomitant sensory activation. This is a relevant topic that the TMSeEEG community has previously identified [2] and addressed with different strategies [3e6]. Based on the similarity of the evoked EEG responses they obtained in real TMS at different sites and in sham conditions (auditory and somatosensory scalp stimulation), the authors of [1] inferred that TEPs can be significantly contaminated by the effects of concurrent, non-transcranial stimulation.We acknowledge this is a valuable reminder to the TMS-EEG community; however, we contend that another fundamental implication of the work by Conde, Tomasevic and colleagues [1] -only incidentally mentioned at the end of their discussion e is that the evoked responses they obtain from both real TMS and sham conditions are substantially different from the TEPs reported in many of the previous studies (see, for example [7e11]). This discrepancy offers a timely opportunity to focus on the issue of the reproducibility of TEPs across laboratories and, most important, can encourage a constructive debate within the whole TMSeEEG community towards the optimization of shared procedures to obtain genuine responses to TMS.In this vein, Fig. 1 directly compares the TEPs reported in Ref.[1] with others previously published in different studies taken as a reference by Conde, Tomasevic and colleagues [1].The inspection of Fig. 1 clearly shows that it is possible to effectively trigger high-amplitude, sharply rising early (<50 ms) components and overall TEP wave-shapes that are specific for the angle and site of stimulation and that are very different from those obtained in Ref. [1]. This simple comparison highlights a general problem of reproducibility and offers an excellent opportunity to discuss two critical steps in TMSeEEG data acquisition: (i) maximising the impact of TMS on the cortex, and (ii) minimizing EEG confounding factors due to sensory co-stimulation.Regarding the impact of TMS on the cortex, it is very likely that the authors of [1] were not as effective as other investigators for the following reasons. First, they applied TMS with a maximum electric field (E-field) intensity between 70 and 90 V/m according to their estimation, assuming a priori that this would have warranted effective cortical activation based on a previous work [12]. However, in Ref. [1] the authors adopted a small coil (outer winding diameter: 45 mm) which, compared to the larger ones (outer winding

The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex

“…Furthermore, selecting an adequate stimulation intensity is important for optimising signal-to-noise ratios of early TEP peaks. While we did use anatomical MRI scans to individualise coil placement and observed differences in the scalp topography and source localisation of the early TEP peaks between stimulation sites, we did not check TEP amplitudes online to optimise stimulation intensity and minimise muscle artifact, a method which has recently been advocated to improve signal-to-noise in TMS-EEG recordings 11 . As a result, the early TEP peaks in this study are smaller than those observed by other groups stimulating similar regions 6 .…”

“…However, several recent studies have shown that residual auditory and somatosensory activity resulting from the TMS pulse also contributes to TEPs under certain circumstances despite experimental measures designed to minimise sensory inputs such as auditory masking and foam padding 9,10 . Such findings highlight the need for careful experimental set-up 11 and control conditions 12 in TMS-EEG studies. In support of the excitation/inhibition hypothesis, pharmacological agonists of inhibitory neurotransmission mediated by fast activating γ-aminobutyric acid (GABA)-A receptors given at sub-anaesthetic doses increase the amplitude of early TEPs (e.g.…”

Pinging the Brain with Transcranial Magnetic Stimulation Reveals Cortical Reactivity in Time and Space

“…Specifically, sham TMS elicited EEG potentials that were correlated highly with those by real TMS, despite the use of sophisticated procedures to attenuate the somatosensory and auditory confounds. In rebuttal of this publication, it was suggested that insufficient TMS intensity and incomplete auditory masking may explain the sensory-dominant evoked potentials in the experiment[4]. Nonetheless, residual auditory input is unavoidable in TMS studies[5] because of air and bone conduction from the TMS clicking sound[6,7].…”

Measures of states of consciousness during attentional and cognitive load

“…However, the PCI measure has shown similar values in the dreaming state, when one is presumably unconscious of the TMS stimulations, as in the awake state (Casarotto et al, 2016) . Therefore, it seems improbable that attention towards sensory aspects of TMS stimulation affects PCI, when the TMS-EEG procedure is properly executed (Belardinelli et al, 2019) . However, there is an alternative hypothesis: the observed difference in response to auditory pattern irregularities (P3b) might not only be modulated by attentional focus but also by the cognitive load and the use of attentional resources demanded by the task itself.…”