Probing regional cortical excitability via input–output properties using transcranial magnetic stimulation and electroencephalography coupling

Abstract

The modular organization of the cortex refers to subsets of highly interconnected nodes, sharing specific cytoarchitectural and dynamical properties. These properties condition the level of excitability of local pools of neurons. In this study, we described TMS evoked potentials (TEP) input–output properties to provide new insights into regional cortical excitability. We combined robotized TMS with EEG to disentangle region‐specific TEP from threshold to saturation and describe their oscillatory contents. Twenty‐two young healthy participants received robotized TMS pulses over the right primary motor cortex (M1), the right dorsolateral prefrontal cortex (DLPFC) and the right superior occipital lobe (SOL) at five stimulation intensities (40, 60, 80, 100, and 120% resting motor threshold) and one short‐interval intracortical inhibition condition during EEG recordings. Ten additional subjects underwent the same experiment with a realistic sham TMS procedure. The results revealed interregional differences in the TEPs input–output functions as well as in the responses to paired‐pulse conditioning protocols, when considering early local components (<80 ms). Each intensity in the three regions was associated with complex patterns of oscillatory activities. The quality of the regression of TEPs over stimulation intensity was used to derive a new readout for cortical excitability and dynamical properties, revealing lower excitability in the DLPFC, followed by SOL and M1. The realistic sham experiment confirmed that these early local components were not contaminated by multisensory stimulations. This study provides an entirely new analytic framework to characterize input–output relations throughout the cortex, paving the way to a more accurate definition of local cortical excitability.

Recording brain responses to TMS of primary motor cortex by EEG – utility of an optimized sham procedure

“…This can also be inferred from the low amplitude of the EEG response evoked by this condition, which led to a N100 potential in frontocentral regions following real TMS, most likely representing a residual PEP that was not adequately controlled for by the sham condition ( Rocchi et al., 2021 ). One example of a more adequate control for somatosensory inputs is reported by Raffin et al. (2020) , who analyzed the EEG responses to increasing TMS intensities, while also attempting to match the sensory input by increasing ES intensities ( Raffin et al., 2020 ).…”

“…One example of a more adequate control for somatosensory inputs is reported by Raffin et al. (2020) , who analyzed the EEG responses to increasing TMS intensities, while also attempting to match the sensory input by increasing ES intensities ( Raffin et al., 2020 ).…”

“…In TMS-EEG experiments, the sham condition must also reliably control for the peripherally evoked responses in the EEG caused by real TMS. Several procedures have been proposed to clear TMS-EEG data from PEPs, including ICA, and linear regression or cosine similarity-based analysis ( Biabani et al., 2019 ; Freedberg et al., 2020 ; Raffin et al., 2020 ). However, these methods do not exempt the need of a sham condition, as it is necessary to inform the models what constitutes a PEP, so it can then be removed from the real TMS response.…”

“…An even more far-reaching assumption is that the TEPs and PEPs are independent phenomena and do not exert any influence on each other, meaning that their corresponding EEG signals are simply linearly superimposed. This assumption is the basis of most proposed methods so far to remove PEPs from TMS-EEG responses ( Biabani et al., 2019 ), and also necessary for statistical comparisons between real and sham TMS conditions, as they have been widely performed in previous studies ( Herring et al., 2015 ; ter Braack et al., 2015 ; Du et al., 2017 ; Gordon et al., 2018 ; Raffin et al., 2020 ; Rocchi et al., 2021 ). However, the assumption that TEPs and PEPs do not interact is unlikely, given the converging evidence for modulatory effects of sensory input on motor cortex excitability ( Novembre et al., 2019 ) (for review ( Kenemans, 2015 ; Wessel and Aron, 2017 )).…”

Temporally-precise disruption of prefrontal cortex informed by the timing of beta bursts impairs human action-stopping

“…Resting motor threshold (RMT) was defined as the lowest intensity to evoke an MEP of at least 0.05 mV in 5 of 10 consecutive trials while participants were at rest. We then established the stimulus intensity to be used during task for the TMS Real coil, which was set to 120% RMT – a level capable of evoking substantial activity in prefrontal cortex ( Raffin et al, 2020 ; Zrenner et al, 2020 ). The real TMS coil was them moved to the pars opercularis target site ( Fig.…”