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

Valdas Noreika,Marc R Kamke,Andrés Canales-Johnson,Srivas Chennu,Tristan A Bekinschtein,Jason B Mattingley

doi:10.1016/j.neuroimage.2020.117305

Abstract

Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation can vary substantially between participants and even from trial to trial within individuals. Recent work from resting state functional magnetic resonance imaging (fMRI) studies has suggested that spontaneous fluctuations in alertness over a testing session can modulate the neural dynamics of cortical processing, even when participants remain awake and responsive to the task at hand. Here we investigated the extent to which spontaneous fluctuations in alertness during wake-to-sleep transition can account for the variability in neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked responses with decreasing levels of alertness, even while participants remained responsive in the behavioural task. Specifically, we found that the amplitude of motor evoked potentials peaked during periods of EEG flattening, whereas TMS-evoked potentials increased and remained stable during EEG flattening and the subsequent occurrence of theta ripples that indicate the onset of NREM stage 1 sleep. Our findings suggest a rapid and complex reorganization of active neural networks in response to spontaneous fluctuations of alertness over relatively short periods of behavioural testing during wake-to-sleep transition.

Highlights

Transcranial magnetic stimulation (TMS) is widely used for probing human brain function in health and disease (Dugué and VanRullen, 2017; Valero-Cabré et al, 2017; Ziemann, 2017)
All participants ceased responding at some point during the testing session, after which they were either aroused spontaneously due to TMS, or they were prompted by an experimenter after 3 consecutive unresponsive trials
Most studies that use TMS to investigate perceptual, cognitive and motor function in human participants do not consider the possibility that fluctuating levels of alertness across a single daytime testing session might lead to measurable changes in the associated patterns of brain activity

Summary

Introduction

Transcranial magnetic stimulation (TMS) is widely used for probing human brain function in health and disease (Dugué and VanRullen, 2017; Valero-Cabré et al, 2017; Ziemann, 2017). A number of neurophysiological indices of cortical TMS perturbation have been used to contrast experimental conditions of interest, including motor evoked potentials (MEPs) recorded from peripheral muscles (Barker et al, 1985; Bestmann and Krakauer, 2015) and TMS-evoked potentials (TEPs) which are thought to reflect the reactivity of underlying cortical circuits (Chung et al, 2015; Ilmoniemi et al, 1997). Sleep pressure has been shown to modulate TMS responses during normal waking in daytime hours (e.g., De Gennaro et al, 2007; Huber et al, 2013). It remains unknown, whether the effects of TMS on

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