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Edited by Terrence J. Sejnowski, Salk Institute for Biological Studies, La Jolla, CA, and approved October 13, 2015 (received for review July 12, 2015)
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.
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.
Intrinsic excitability measures
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