An analytical approach to identify indirect multisensory cortical activations elicited by TMS?

Electroencephalography (EEG) is widely used for detecting transcranial-magnetic stimulation (TMS) evoked responses in the human brain. TMS-evoked potentials (TEPs) may contain both direct activations due to TMS-induced cortical electric field and indirect subsequent multisensory TMS [[1]Ilmoniemi R.J. Kičić D. Methodology combined EEG.Brain Topogr. 2009; 22: 233-248Crossref PubMed Scopus (204) Google Scholar]. Distinguishing between sources of activation has largely been attempted using careful experimental designs [2Biabani M. Fornito A. Mutanen T.P. Morrow J. Rogasch N.C. Characterizing minimizing contribution sensory inputs potentials.Brain Stimul. 2019; 12: 1537-1552Abstract Full Text PDF (21) Scholar, 3Rocchi L. Di Santo Brown K. Ibáñez Casula E. Rawji V. Lazzaro Koch G. Rothwell Disentangling EEG peripheral activations.Brain 2021; 14: 4-18Abstract (13) 4Conde Tomasevic Akopian I. Stanek Saturnino G.B. Thielscher Bergmann T.O. Siebner H.R. The non-transcranial potential an inherent source ambiguity TMS-EEG studies.Neuroimage. 185: 300-312Crossref (84) 5Gordon P.C. Desideri Belardinelli P. Zrenner C. Ziemann U. Comparison realistic sham versus real motor cortex.Brain 2018; 11: 1322-1330Abstract (28) Here, we complement those advances by providing a novel statistical approach. Our results converge with pattern identified recent work [[3]Rocchi Scholar], which provides encouraging support utility this Several different strategies have deal response stimulation. One approach suppress consequently minimize activations. This powerfully illustrated study, sound coil was very efficiently masked playing noise-masking via earplugs as well ear defenders, vibrations were attenuated foam layer beneath Whether suppression completely effective debated (e.g. [[4]Conde Scholar,[6]Belardinelli Biabani Blumberger D.M. Bortoletto Casarotto S. David O. Etkin Ferrarelli F. Fitzgerald P.B. et al.Reproducibility TMS–EEG studies: call data sharing, standard procedures control.Brain 787-790Abstract (34) Scholar]). An alternative use mimic, isolate [3Rocchi Yet, requires techniques accurately reproduce elicited Scholar,[4]Conde challenging achieve. Both these approaches manipulations within-subjects. We offer complementary between-subjects analysis indentify Commonly studies, participants receive intensity tailored their individual susceptibility When stimulating primary cortex (M1) called resting-motor threshold (rMT, [[7]Rossini P.M. Burke Chen R. Cohen L.G. Daskalakis Z. Iorio Ferreri George M.S. al.Non-invasive electrical magnetic brain, spinal cord, roots nerves: basic principles routine clinical research application. updated report from I.F.C.N. Committee.Clin Neurophysiol. 2015; 126: 1071-1107Crossref (1100) Scholar]; relative intensity). corresponds percentage stimulator output (absolute For example, one participant 80% rMT require 48% maximum (MSO); while another will be achieved only 36% MSO (Fig. 1A). administered rMT) represents normalization implying that magnitude should comparable across subjects. By contrast, pulse closely related amount input, itself higher absolute vs MSO; i.e., louder sound, stronger vibration, somatosensory fibres). As consequence, design, receiving experience more stimulation, turn display amplitude activation. tested how could explain between-subject variability responses, whether corresponded spatiotemporal earlier analysed pre-existing dataset (58 participants, 41 females, 23 ± 4 years old (mean std); right-handed (defined Edinburgh Handedness Inventory); neurologically psychiatrically normal meeting safety criteria TMS). Participants received 126 neuro-navigated biphasic single TMS-pulses left (M1), (a 62-channel system) concurrently recorded. Stimulation set at participants’ ([[7]Rossini 54 8% std), range 31 77% MSO). Individually adjusted white noise (the volume gradually increased until not hear click anymore or discomfort reached) played during padded earplugs. In our analysis, concentrated on most commonly assessed dimension signal (i.e., TEPs Fig. 1B). Initially, cleaned typical artifacts, MATLAB-based toolbox EEGLAB analyser plugin (TESA [[8]Rogasch Sullivan Thomson R.H. Rose N.S. Bailey N.W. Farzan Hernandez-Pavon J.C. Analysing concurrent transcranial electroencephalographic data: review introduction open-source TESA software.Neuroimage. 2017; 147: 934-951Crossref (86) evaluating spatio-temporal effects intensity, computed (as average time-course over trials) each channel subject separately (in reference). Then, resulting time point (331; i.e. 20 – 350 ms after pulse) (62 channels) linear regression test independent variable, subject-specific can predict TEP (FieldTrip [[9]Oostenveld Fries Maris Schoffelen J.-M. FieldTrip: open software advanced MEG, EEG, invasive electrophysiological data.Comput Intell Neurosci. 2011; 2011: 156869Crossref (4073) To possible significance, ran independent-samples coefficient t-tests (two-tailed, α level p < 0.025). control multiple comparison problem familywise error rate [[10]Maris Oostenveld Nonparametric testing EEG- MEG-data.J Neurosci Methods. 2007; 164: 177-190Crossref (3528) Scholar]), clusters built assembling neighbouring significant samples against corresponding permutation statistics (5000 iterations, cluster 0.025 found showed three clusters. All occurred later latencies. negative showing deflection 1C, bottom row). first positive visible 174–241 mainly involved central electrodes (corrected = 0.025; top second 264–337 located above sensorimotor 0.034, middle Finally, 259–303 left-frontal regions 0.038, Based patterns, caused combination auditory processes These show late (>170 ms) intensity. identify activations, suggests design linked delivering TMS. Despite methodological differences, temporally spatially Hence, analytical method makes identification unconstrained allowing new questions posed innovative designs, previously impossible. further needed fully validate Nonetheless, it prove simple yet tool potentially remove contributions data; without need include additional conditions within study. declare conducted free any commercial financial relationships lead, seen lead conflict interest. are grateful Air Force Office Scientific Research ( FA9550-16-1-0191 ; EMR) Academy Finland (Grant No. 321631 TPM) supporting work.