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February 10, 2015; 84 (6) Article

Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone

Liankun Ren, Michal T. Kucewicz, Jan Cimbalnik, Joseph Y. Matsumoto, Benjamin H. Brinkmann, Wei Hu, W. Richard Marsh, Fredric B. Meyer, S. Matthew Stead, Gregory A. Worrell
First published January 14, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001234
Liankun Ren
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.
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Michal T. Kucewicz
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.
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Jan Cimbalnik
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.
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Joseph Y. Matsumoto
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.
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Benjamin H. Brinkmann
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.
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Wei Hu
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.
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W. Richard Marsh
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.
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Fredric B. Meyer
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.
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S. Matthew Stead
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.
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Gregory A. Worrell
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.
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Citation
Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone
Liankun Ren, Michal T. Kucewicz, Jan Cimbalnik, Joseph Y. Matsumoto, Benjamin H. Brinkmann, Wei Hu, W. Richard Marsh, Fredric B. Meyer, S. Matthew Stead, Gregory A. Worrell
Neurology Feb 2015, 84 (6) 602-608; DOI: 10.1212/WNL.0000000000001234

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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.

GLOSSARY

HFO=
high-frequency oscillation;
IED=
interictal epileptiform discharge;
iEEG=
intracranial EEG;
SOZ=
seizure onset zone

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received May 29, 2014.
  • Accepted in final form October 16, 2014.
  • © 2015 American Academy of Neurology
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