Increased gamma and decreased fast ripple connections of epileptic tissue: A high-frequency directed network approach

Willemiek J.E.M. Zweiphenning*, Hanneke M. Keijzer, Eric van Diessen, Maryse A. van ‘t Klooster, Nicole E.C. van Klink, Frans S.S. Leijten, Peter C. van Rijen, Michel J.A.M. van Putten, Kees P.J. Braun, Maeike Zijlmans

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Objective: New insights into high-frequency electroencephalographic activity and network analysis provide potential tools to improve delineation of epileptic tissue and increase the chance of postoperative seizure freedom. Based on our observation of high-frequency oscillations “spreading outward” from the epileptic source, we hypothesize that measures of directed connectivity in the high-frequency range distinguish epileptic from healthy brain tissue. Methods: We retrospectively selected refractory epilepsy patients with a malformation of cortical development or tumor World Health Organization grade I/II who underwent epilepsy surgery with intraoperative electrocorticography for tailoring the resection based on spikes. We assessed directed functional connectivity in the theta (4-8 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (FR; 250-500 Hz) bands using the short-time direct directed transfer function, and calculated the total, incoming, and outgoing propagation strength for each electrode. We compared network measures of electrodes covering the resected and nonresected areas separately for patients with good and poor outcome, and of electrodes with and without spikes, ripples, and FRs (group level: paired t test; patient level: Mann-Whitney U test). We selected the measure that could best identify the resected area and channels with epileptic events using the area under the receiver operating characteristic curve, and calculated the positive and negative predictive value, sensitivity, and specificity. Results: We found higher total and outstrength in the ripple and gamma bands in resected tissue in patients with good outcome (rippletotal: P =.01; rippleout: P =.04; gammatotal: P =.01; gammaout: P =.01). Channels with events showed lower total and instrength, and higher outstrength in the FR band, and higher total and outstrength in the ripple, gamma, and theta bands (FRtotal: P =.05; FRin: P <.01; FRout: P =.02; gammatotal: P <.01; gammain: P =.01; gammaout: P <.01; thetatotal: P =.01; thetaout: P =.01). The total strength in the gamma band was most distinctive at the channel level (positive predictive value [PPV]good = 74%, PPVpoor = 43%). Significance: Interictally, epileptic tissue is isolated in the FR band and acts as a driver up to the (fast) ripple frequency range. The gamma band total strength seems promising to delineate epileptic tissue intraoperatively.

Original languageEnglish
Pages (from-to)1908-1920
Number of pages13
Issue number9
Early online date22 Jul 2019
Publication statusPublished - 1 Sept 2019


  • UT-Hybrid-D
  • epilepsy
  • epilepsy surgery
  • high-frequency activity
  • high-frequency oscillations
  • network analysis
  • effective connectivity


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