Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges

  1. Elliot H Smith  Is a corresponding author
  2. Jyun-you Liou
  3. Edward M Merricks
  4. Tyler Davis
  5. Kyle Thomson
  6. Bradley Greger
  7. Paul House
  8. Ronald G Emerson
  9. Robert Goodman
  10. Guy M McKhann
  11. Sameer Sheth
  12. Catherine Schevon
  13. John D Rolston  Is a corresponding author
  1. University of Utah, United States
  2. Weill Cornell Medicine, United States
  3. Columbia University Medical Center, United States
  4. Arizona State University, United States
  5. Neurosurgical Associates, LLC, United States
  6. Hospital for Special Surgery, United States
  7. Lenox Hill Hospital, United States
  8. Baylor College of Medicine, United States
  9. Columbia University, United States

Abstract

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Though they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus.

Data availability

Raw data is available upon establishment of a data use agreement with Columbia University Medical Center as required by their Institutional Review Board (IRB). Data from human subjects was analyzed, from which the dates of implants can potentially be reconstructed. This is especially true for a study like this one, in which chronic recordings were carried out for the full duration of the patients' hospital stays. Sharing these data widely could therefore expose private health information of participants, which is why a data use agreement is required by the IRB. Interested Researchers should contact Dr. Schevon to get the data use agreement process started with the Columbia University Medical Center IRB.Analysis code is upload to GitHub: https://github.com/elliothsmith/IEDs. We have included preprocessed data files for all IEDs, hosted online at OSF: https://osf.io/zhk24/. Data files include LFP, MUA event times, and traveling wave model coefficients for all detected IEDs.

The following data sets were generated

Article and author information

Author details

  1. Elliot H Smith

    Department of Neurolosurgery, University of Utah, Salt Lake City, United States
    For correspondence
    e.h.smith@utah.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4323-4643
  2. Jyun-you Liou

    Department of Anesthesiology, Weill Cornell Medicine, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4851-3676
  3. Edward M Merricks

    Department of Neurology, Columbia University Medical Center, New York CIty, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8172-3152
  4. Tyler Davis

    Department of Neurosurgery, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  5. Kyle Thomson

    Departments of Neurosurgery, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  6. Bradley Greger

    Department of Bioengineering, Arizona State University, Tempe, United States
    Competing interests
    No competing interests declared.
  7. Paul House

    Neurosurgical Associates, LLC, Murray, United States
    Competing interests
    Paul House, is affiliated with Neurosurgical Associates, LLC. The author has no financial interests to declare..
  8. Ronald G Emerson

    Hospital for Special Surgery, New York, United States
    Competing interests
    No competing interests declared.
  9. Robert Goodman

    Lenox Hill Hospital, New York, United States
    Competing interests
    No competing interests declared.
  10. Guy M McKhann

    Department of Neurological Surgery, Columbia University Medical Center, New York, United States
    Competing interests
    Guy M McKhann, reports fees from Koh Young, Inc.
  11. Sameer Sheth

    Department of Neurological Surgery, Baylor College of Medicine, Houston, United States
    Competing interests
    Sameer Sheth, consulting for Boston Scientific, Abbott, Neuropace, Zimmer Biomet..
  12. Catherine Schevon

    Department of Neurology, Columbia University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4485-7933
  13. John D Rolston

    Departments of Neurosurgery, University of Utah, Salt Lake City, United States
    For correspondence
    john.rolston@utah.edu
    Competing interests
    John D Rolston, reports fees from Medtronic, Inc..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8843-5468

Funding

National Institutes of Health (NINDS R21 NS113031)

  • Elliot H Smith
  • Catherine Schevon
  • John D Rolston

National Institutes of Health (NINDS K23 NS114178)

  • John D Rolston

National Institutes of Health (S10 OD018211)

  • Catherine Schevon

National Institutes of Health (R01 NS084142)

  • Catherine Schevon

American Epilepsy Society (JIA)

  • Elliot H Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matthew Shtrahman, University of California, San Diego, United States

Ethics

Human subjects: The Institutional Review Boards at the University of Utah (IRB_00114691) and Columbia University Medical Center (IRB- AAAB6324) approved these studies. All participants provided informed consent prior to surgery for implantation of the clinical and research electrodes.

Version history

  1. Preprint posted: April 29, 2021 (view preprint)
  2. Received: September 2, 2021
  3. Accepted: January 19, 2022
  4. Accepted Manuscript published: January 20, 2022 (version 1)
  5. Accepted Manuscript updated: January 24, 2022 (version 2)
  6. Version of Record published: February 3, 2022 (version 3)

Copyright

© 2022, Smith et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Elliot H Smith
  2. Jyun-you Liou
  3. Edward M Merricks
  4. Tyler Davis
  5. Kyle Thomson
  6. Bradley Greger
  7. Paul House
  8. Ronald G Emerson
  9. Robert Goodman
  10. Guy M McKhann
  11. Sameer Sheth
  12. Catherine Schevon
  13. John D Rolston
(2022)
Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges
eLife 11:e73541.
https://doi.org/10.7554/eLife.73541

Share this article

https://doi.org/10.7554/eLife.73541

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