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

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 t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-11, Vol.112 (47), p.14694-14699
Main Authors: Meisel, Christian, Schulze-Bonhage, Andreas, Freestone, Dean, Cook, Mark James, Achermann, Peter, Plenz, Dietmar
Format: Article
Language:English
Subjects:
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Biological Sciences
Convulsions & seizures
Correlation analysis
Cortical Synchronization - drug effects
Electric Stimulation
Epilepsy
Epilepsy - drug therapy
Epilepsy - physiopathology
Humans
Male
Physical Sciences
Prescription drugs
Seizures - drug therapy
Sleep
Sleep - drug effects
Sleep - physiology
Time Factors
Wakefulness - drug effects
Wakefulness - physiology
Young Adult
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1513716112