Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Christian Meisel, Andreas Schulze-Bonhage, Dean Freestone, Mark James Cook, Peter Achermann, and Dietmar Plenz
PNAS first published November 9, 2015; https://doi.org/10.1073/pnas.1513716112
Christian Meisel
aSection on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: christian@meisel.de
Andreas Schulze-Bonhage
bEpilepsy Center, Neurocenter, University Medical Center Freiburg, 79106 Freiburg, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dean Freestone
cDepartment of Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC 3010, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark James Cook
dDepartment of Neurology, St. Vincent’s Hospital, Melbourne, University of Melbourne, Fitzroy, VIC 3065, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Achermann
eInstitute of Pharmacology and Toxicology, University of Zurich, 8006 Zurich, Switzerland;
fNeuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland;
gZurich Center for Interdisciplinary Sleep Research, University of Zurich, 8057 Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dietmar Plenz
aSection on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Terrence J. Sejnowski, Salk Institute for Biological Studies, La Jolla, CA, and approved October 13, 2015 (received for review July 12, 2015)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Dynamic changes of cortical excitability are relevant in both healthy and pathological network dynamics. In epilepsy, pathological changes in excitability commonly underlie the initiation and spread of seizures. Accordingly, the ability to monitor excitability and control its degree is important for adequate clinical care and treatment because classic EEG markers found in epilepsy such as interictal spikes do not reflect seizure propensity and thus excitability. Here, we identify excitability markers and test them on long-term electrocorticogram and EEG recordings. We show that they correlate with more direct excitability measures using external stimulation and allow for real-time excitability monitoring. Our results provide evidence that excitability of cortical networks is reduced by antiepileptic drugs and increases as a function of time awake.

Abstract

Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.

  • excitability
  • epilepsy
  • sleep

Footnotes

  • ↵1To whom correspondence should be addressed. Email: christian{at}meisel.de.
  • Author contributions: C.M. designed research; C.M., A.S.-B., M.J.C., and P.A. performed research; C.M., A.S.-B., D.F., M.J.C., and P.A. contributed new reagents/analytic tools; C.M. analyzed data; and C.M., A.S.-B., and D.P. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1513716112/-/DCSupplemental.

Freely available online through the PNAS open access option.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Intrinsic excitability measures
Christian Meisel, Andreas Schulze-Bonhage, Dean Freestone, Mark James Cook, Peter Achermann, Dietmar Plenz
Proceedings of the National Academy of Sciences Nov 2015, 201513716; DOI: 10.1073/pnas.1513716112

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Intrinsic excitability measures
Christian Meisel, Andreas Schulze-Bonhage, Dean Freestone, Mark James Cook, Peter Achermann, Dietmar Plenz
Proceedings of the National Academy of Sciences Nov 2015, 201513716; DOI: 10.1073/pnas.1513716112
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (3)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490