title: EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time.
abstract: BACKGROUND
  High-density electroencephalography (hd-EEG) combined with transcranial magnetic stimulation (TMS) provides a direct and non-invasive measure of cortical excitability and connectivity in humans and may be employed to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. However, the diagnostic/monitoring applications of this technique would be limited to the extent that TMS-evoked potentials are either stereotypical (non-sensitive) or random (non-repeatable) responses. Here, we used controlled changes in the stimulation parameters (site, intensity, and angle of stimulation) and repeated longitudinal measurements (same day and one week apart) to evaluate the sensitivity and repeatability of TMS/hd-EEG potentials.
  
  
  RESULTS
  In 10 volunteers, we performed 92 single-subject comparisons to evaluate the similarities/differences between pairs of TMS-evoked potentials recorded in the same/different stimulation conditions. For each pairwise comparison, we used non-parametric statistics to calculate a Divergence Index (DI), i.e., the percentage of samples that differed significantly, considering all scalp locations and the entire post-stimulus period. A receiver operating characteristic analysis showed that it was possible to find an optimal DI threshold of 1.67%, yielding 96.7% overall accuracy of TMS/hd-EEG in detecting whether a change in the perturbation parameters occurred or not.
  
  
  CONCLUSIONS
  These results demonstrate that the EEG responses to TMS essentially reflect deterministic properties of the stimulated neuronal circuits as opposed to stereotypical responses or uncontrolled variability. To the extent that TMS-evoked potentials are sensitive to changes and repeatable over time, they may be employed to detect longitudinal changes in the state of cortical circuits.
authors.affiliation: Department of Clinical Sciences L Sacco, Università degli Studi di Milano, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Casarotto
authors.forename: Leonor J
authors.initials: LJ
authors.lastname: Romero Lauro
authors.forename: Valentina
authors.initials: V
authors.lastname: Bellina
authors.forename: Adenauer G
authors.initials: AG
authors.lastname: Casali
authors.forename: Mario
authors.initials: M
authors.lastname: Rosanova
authors.forename: Andrea
authors.initials: A
authors.lastname: Pigorini
authors.forename: Stefano
authors.initials: S
authors.lastname: Defendi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mariotti
authors.forename: Marcello
authors.initials: M
authors.lastname: Massimini
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D012372:ROC Curve; D012680:Sensitivity and Specificity; D050781:Transcranial Magnetic Stimulation / Q000379:methods*