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Author Notes:

Corresponding Author: Robert E. Gross, Department of Neurosurgery, Emory University School of Medicine, 1365B Clifton Road, NE, Suite 6200, Atlanta, GA 30322 (USA), rgross@emory.edu

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of Interest: None of the authors have conflicts of interest to declare. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.


Research Funding:

This work was funded by the Wallace H. Coulter Foundation (http://www.whcf.org/), the Epilepsy Research Foundation (http://www.epilepsy.com/etp/scientific_research), a Neurology/Biomedical Engineering seed grant from Emory University and Georgia Tech (http://www.bme.gatech.edu/), a University Research Council grant from Emory University (http://www.emory.edu), the National Institute of General Medical Sciences (NIGMS; http://www.nigms.nih.gov/) to JDR and NGL (GM08169), and, from the National Institute of Neurological Disorders and Stroke (NINDS; http://www.ninds.nih.gov/), a Ruth L. Kirschstein National Research Service Award to JDR (NS060392), a translational research fellowship to JDR (NS007480), a career development award to REG (NS046322), and a research grant to SMP and REG (NS054809).


  • Oscillations
  • microelectrode
  • stimulation
  • interictal spike
  • electrocorticography
  • animal model

Spontaneous and Evoked High Frequency Oscillations in the Tetanus Toxin Model of Epilepsy


Journal Title:



Volume 51, Number 11


, Pages 2289-2296

Type of Work:

Article | Post-print: After Peer Review


Summary Purpose High-frequency oscillations (HFOs) are an emerging biomarker for epileptic tissue. Yet the mechanism by which HFOs are produced is unknown, and their rarity makes them difficult to study. Our objective was to examine the occurrence of HFOs in relation to action potentials (APs) and the effect of microstimulation in the tetanus toxin (TT) model of epilepsy, a non-lesional model with a short latency to spontaneous seizures. Methods Rats were injected with TT into dorsal hippocampus and implanted with a 16 channel (8 × 2) multielectrode array, one row each in CA3 and CA1. After onset of spontaneous seizures (3-9 days), recordings were begun of APs and local field potentials, analyzed for the occurrence of interictal spikes and HFOs. Recordings were made during microstimulation of each electrode using customized, open-source software. Results Population bursts of APs during interictal spikes were phase-locked with HFOs, which were observable almost exclusively with high-amplitude interictal spikes. Further, HFOs could reliably be produced by microstimulation of the hippocampus, providing evidence that these oscillations can be controlled temporally by external means. Discussion We show for the first time the occurrence of HFOs in the TT epilepsy model, an attractive preparation for their experimental investigation and, importantly, one with a different etiology than status models, providing further evidence of the generality of HFOs. The ability to provoke HFOs with microstimulation may prove useful for better understanding HFOs by directly evoking them in the lab, and designing high-throughput techniques for pre-surgical localization of the epileptic focus.

Copyright information:

©2010 International League Against Epilepsy

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