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On the Cerebral Origin of EEG Responses to TMS: Insights From Severe Cortical Lesions

Published:October 17, 2014DOI:https://doi.org/10.1016/j.brs.2014.10.008

      Highlights

      • TMS-evoked potentials (TEPs) are absent when cortical lesions are stimulated.
      • TEPs can be recorded only when functional cortical regions are targeted.
      • When proper procedures are applied, TEPs purely reflect cortical responses to TMS.
      • To reliably assess brain-injured patients, neuronavigated TMS is needed.

      Abstract

      Background

      Transcranial magnetic stimulation combined with electroencephalography (TMS/EEG) represents a valuable tool to probe cortical excitability and connectivity. Although several procedures have been devised to abolish TMS-related artifacts, direct evidence that it is possible to record TMS-evoked potentials (TEPs) that purely reflect cortical responses to TMS are still lacking.

      Objective

      To demonstrate that when TMS is delivered on a human head with intact nerves, scalp and ocular muscles, TEPs are present only if a functional portion of cortex is targeted and is absent otherwise.

      Methods

      We performed extensive navigated TMS/EEG mappings in three vegetative state patients and in eight healthy controls. Patients were selected based on the extension of their cortical lesions as revealed by structural/functional imaging: the cerebral cortex was globally damaged in Patient 1 due to cerebral anoxia, Patient 2 showed a traumatic damage affecting one cerebral hemisphere, while Patient 3 was characterized by one left sided and one right-sided focal ischemic lesion.

      Results

      In Patient 1, TMS performed at any targeted cortical site did not elicit statistically significant TEPs. In Patient 2, TEPs were absent when the damaged hemisphere was targeted, while were present over the healthy side. In Patient 3, significant TEPs were absent when cortical lesions were targeted and present otherwise. Significant TEPs were always present in healthy controls.

      Conclusions

      These findings suggest that, provided that appropriate experimental procedures are employed, TEPs are genuine cortical responses detectable only when preserved cortical tissue is stimulated. Hence, a dependable assessment of cortical excitability and connectivity in brain-injured patients requires the use of neuronavigated TMS.

      Keywords

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      References

        • Miniussi C.
        • Thut G.
        Combining TMS and EEG offers new prospects in cognitive neuroscience.
        Brain Topogr. 2010; 22: 249-256
        • Rogasch N.C.
        • Fitzgerald P.B.
        Assessing cortical network properties using TMS-EEG.
        Hum Brain Mapp. 2013; 34: 1652-1669
        • Ziemann U.
        Transcranial magnetic stimulation at the interface with other techniques: a powerful tool for studying the human cortex.
        Neuroscientist. 2011; 17: 368-381
        • Ilmoniemi R.J.
        • Virtanen J.
        • Ruohonen J.
        • et al.
        Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity.
        Neuroreport. 1997; 8: 3537-3540
        • Virtanen J.
        • Ruohonen J.
        • Näätänen R.
        • Ilmoniemi R.J.
        Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation.
        Med Biol Eng Comput. 1999; 37: 322-326
        • Ilmoniemi R.J.
        • Kičić D.
        Methodology for combined TMS and EEG.
        Brain Topogr. 2010; 22: 233-248
        • Rosanova M.
        • Gosseries O.
        • Casarotto S.
        • et al.
        Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.
        Brain. 2012; 135: 1308-1320
        • Giacino J.T.
        • Kalmar K.
        • Whyte J.
        The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility.
        Arch Phys Med Rehabil. 2004; 85: 2020-2029
        • Schnakers C.
        • Majerus S.
        • Giacino J.
        • et al.
        A French validation study of the Coma Recovery Scale-Revised (CRS-R).
        Brain Inj. 2008; 22: 786-792
        • Ammermann H.
        • Kassubek J.
        • Lotze M.
        • et al.
        MRI brain lesion patterns in patients in anoxia-induced vegetative state.
        J Neurol Sci. 2007; 260: 65-70
        • Bruno M.A.
        • Majerus S.
        • Boly M.
        • et al.
        Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
        J Neurol. 2012; 259: 1087-1098
        • Bruno M.A.
        • Vanhaudenhuyse A.
        • Schnakers C.
        • et al.
        Visual fixation in the vegetative state: an observational case series PET study.
        BMC Neurol. 2010; 10: 35
        • Thibaut A.
        • Bruno M.A.
        • Chatelle C.
        • et al.
        Metabolic activity in external and internal awareness networks in severely brain-damaged patients.
        J Rehabil Med. 2012; 44: 487-494
        • Mutanen T.
        • Maki H.
        • Ilmoniemi R.J.
        The effect of stimulus parameters on TMS-EEG muscle artifacts.
        Brain Stimul. 2012; 6: 371-376
        • Casali A.G.
        • Casarotto S.
        • Rosanova M.
        • Mariotti M.
        • Massimini M.
        General indices to characterize the electrical response of the cerebral cortex to TMS.
        Neuroimage. 2010; 49: 1459-1468
        • Komssi S.
        • Savolainen P.
        • Heiskala J.
        • Kahkonen S.
        Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography.
        Neuroreport. 2007; 18: 13-16
        • Rosanova M.
        • Casali A.
        • Bellina V.
        • Resta F.
        • Mariotti M.
        • Massimini M.
        Natural frequencies of human corticothalamic circuits.
        J Neurosci. 2009; 29: 7679-7685
        • Ferrarelli F.
        • Massimini M.
        • Sarasso S.
        • et al.
        Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness.
        Proc Natl Acad U S A. 2010; 107: 2681-2686
        • Massimini M.
        • Ferrarelli F.
        • Huber R.
        • Esser S.K.
        • Singh H.
        • Tononi G.
        Breakdown of cortical effective connectivity during sleep.
        Science. 2005; 309: 2228-2232
        • Nikouline V.
        • Ruohonen J.
        • Ilmoniemi R.
        The role of the coil click in TMS assessed with simultaneous EEG.
        Clin Neurophysiol. 1999; 110: 1325-1328
        • Ter Braack E.M.
        • de Vos C.C.
        • van Putten J.A.M.
        Masking the auditory evoked potential in TMS-EEG: a comparison of various methods.
        Brain Topogr. 2013; ([Epub ahead of print])https://doi.org/10.1007/s10548-013-0312-z
        • Lehmann D.
        • Skrandies W.
        Reference-free identification of components of checkerboard-evoked multichannel potential fields.
        Electroencephalogr Clin Neurophysiol. 1980; 48: 609-621
        • Delorme A.
        • Makeig S.
        EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.
        J Neurosci Methods. 2004; 134: 9-21
        • Lv J.
        • Simpson D.M.
        • Bell S.L.
        Objective detection of evoked potentials using a bootstrap technique.
        Med Eng Phys. 2007; 29: 191-198
        • McCubbin J.
        • Yee T.
        • Vrba J.
        • et al.
        Bootstrap significance of low SNR evoked response.
        J Neurosci Methods. 2008; 168: 265-272
        • Laureys S.
        • Celesia G.G.
        • Cohadon F.
        • et al.
        Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome.
        BMC Med. 2010; 8: 68
        • Laureys S.
        • Owen A.M.
        • Schiff N.D.
        Brain function in coma, vegetative state, and related disorders.
        Lancet Neurol. 2004; 3: 537-546
        • Veniero D.
        • Bortoletto M.
        • Miniussi C.
        TMS-EEG co-registration: on TMS-induced artifact.
        Clin Neurophysiol. 2009; 120: 1392-1399
        • Corthout E.
        • Uttl B.
        • Juan C.H.
        • Hallett M.
        • Cowey A.
        Suppression of vision by transcranial magnetic stimulation: a third mechanism.
        Neuroreport. 2000; 11: 2345-2349