title: On the cerebral origin of EEG responses to TMS: insights from severe cortical lesions.
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.
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium; Postle Laboratory and Center for Sleep and Consciousness, Department of Psychiatry and Psychology, University of Wisconsin, Madison, WI, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gosseries
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sarasso
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Casarotto
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Boly
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schnakers
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Napolitani
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Marie-Aurélie
authors.initials: MA
authors.lastname: Bruno
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Ledoux
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Jean-Flory
authors.initials: JF
authors.lastname: Tshibanda
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy; IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Massimini
authors.affiliation: Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
authors.affiliation: Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy; Fondazione Europea di Ricerca Biomedica, FERB Onlus, Milan, Italy. Electronic address: mario.rosanova@unimi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosanova
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology* / Q000502:physiology* / Q000503:physiopathology; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018458:Persistent Vegetative State / Q000473:pathology* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
keywords: Biological artifacts; Brain-injury; Electroencephalography; Transcranial magnetic stimulation