title: Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle.
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.
authors.affiliation: Section on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892; christian@meisel.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.affiliation: Epilepsy Center, Neurocenter, University Medical Center Freiburg, 79106 Freiburg, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze-Bonhage
authors.affiliation: Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC 3010, Australia;
authors.forename: Dean
authors.initials: D
authors.lastname: Freestone
authors.affiliation: Department of Neurology, St. Vincent's Hospital, Melbourne, University of Melbourne, Fitzroy, VIC 3065, Australia;
authors.forename: Mark James
authors.initials: MJ
authors.lastname: Cook
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, 8006 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, 8057 Zurich, Switzerland; Zurich Center for Interdisciplinary Sleep Research, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Achermann
authors.affiliation: Section on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892;
authors.forename: Dietmar
authors.initials: D
authors.lastname: Plenz
mesh_terms: D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D003344:Cortical Synchronization / Q000187:drug effects; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D012640:Seizures / Q000188:drug therapy; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: epilepsy; excitability; sleep