title: Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone.
abstract: OBJECTIVE
  To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG.
  
  
  METHODS
  Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes were analyzed using time-frequency spectral analysis.
  
  
  RESULTS
  Gamma frequency oscillations (30-100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro- and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p < 0.001) and slightly higher frequency (p = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30-100 Hz) and higher (100-600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ.
  
  
  CONCLUSIONS
  The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies.
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Liankun
authors.initials: L
authors.lastname: Ren
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Michal T
authors.initials: MT
authors.lastname: Kucewicz
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Cimbalnik
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Matsumoto
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Brinkmann
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: W Richard
authors.initials: WR
authors.lastname: Marsh
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Meyer
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: S Matthew
authors.initials: SM
authors.lastname: Stead
authors.affiliation: From the Mayo Systems Electrophysiology Laboratory, Department of Neurology (L.R., M.T.K., J.C., J.Y.M., B.H.B., W.H., S.M.S., G.A.W.), and Department of Neurosurgery (W.R.M., F.B.M.), Mayo Clinic, Rochester, MN; Department of Neurology (L.R.), China-Japan Friendship Hospital, Beijing, China; and International Clinical Research Center (J.C.), St. Anne's University Hospital, Brno, Czech Republic. worrell.gregory@mayo.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Worrell
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000295:instrumentation / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D012640:Seizures / Q000503:physiopathology*; D013051:Spectrometry, Gamma