The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies

Virginia Conde,Leo Tomasevic,Irina Akopian,Konrad Stanek,Guilherme B Saturnino,Axel Thielscher,Til Ole Bergmann,Hartwig Roman Siebner

doi:10.1016/j.neuroimage.2018.10.052

Abstract

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud “click” sound, the TMS-evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS-EEG studies to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

Highlights

Transcranial magnetic stimulation (TMS) produces a time-varying electric field that can directly excite neuronal populations in the cortical target area, bypassing the afferent sensory systems (Barker et al, 1985)
We recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real Transcranial Magnetic Stimulation (TMS)
TMS was increased by 5% of maximum stimulator output (MSO) in the sham condition relative to the corresponding real TMS condition

Summary

Introduction

Transcranial magnetic stimulation (TMS) produces a time-varying electric field that can directly excite neuronal populations in the cortical target area, bypassing the afferent sensory systems (Barker et al, 1985). Electroencephalography (EEG) has been increasingly employed in recent years to measure the cortical responses evoked by focal TMS which, thanks to its excellent temporal resolution, can reveal how the local neural response spreads from the target site to functionally and structurally connected brain regions (Bergmann et al, 2016; Bortoletto et al, 2015; Ilmoniemi et al, 1997; Siebner et al, 2009). Connectivity measures have been derived from TMS-EEG data to infer how neuronal activations propagate across specific networks and how these networks change depending on different brain states (Bortoletto et al, 2015; Rosanova et al, 2009). TMS-EEG has been combined with pharmacological interventions to elucidate the mechanisms underlying the different TEP components (Darmani et al, 2016; Premoli et al, 2014a)

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Results

Conclusion