title: Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of Elevated Excitability in the Human Epileptic Brain.
abstract: BACKGROUND
  Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs.
  
  
  OBJECTIVE
  To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses.
  
  
  METHODS
  In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7).
  
  
  CONCLUSIONS
  In GGE, the interictal period contains multiple, quasi-stable covert states of excitability a class of which is associated with the generation of TMS-induced EDs. The relevance of these findings to theoretical models of ictogenesis is discussed.
authors.affiliation: Laboratory of Clinical Neurophysiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Vasilios K
authors.initials: VK
authors.lastname: Kimiskidis
authors.affiliation: Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Koutlis
authors.affiliation: Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Tsimpiris
authors.affiliation: Kuopio Epilepsy Center, Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Reetta
authors.initials: R
authors.lastname: Kälviäinen
authors.affiliation: Department of Functional Neurology and Epileptology, Hospices Civils de Lyon, Lyon, France.|Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.affiliation: Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kugiumtzis
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001921:Brain / Q000503:physiopathology*; D015331:Cohort Studies; D004569:Electroencephalography / Q000379:methods*; D004829:Epilepsy, Generalized / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
keywords: Transcranial magnetic stimulation; brain dynamics; complexity; electroencephalography; genetic generalized epilepsy; idiopathic generalized epilepsy