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Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14694-9. doi: 10.1073/pnas.1513716112. Epub 2015 Nov 9.

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

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Section on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892;
Epilepsy Center, Neurocenter, University Medical Center Freiburg, 79106 Freiburg, Germany;
Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, VIC 3010, Australia;
Department of Neurology, St. Vincent's Hospital, Melbourne, University of Melbourne, Fitzroy, VIC 3065, Australia;
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.
Section on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, MD 20892;


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.


epilepsy; excitability; sleep

[Indexed for MEDLINE]
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