Fast ripples reflect increased excitability that primes epileptiform spikes.

Abstract

The neuronal circuit disturbances that drive interictal and ictal epileptiform discharges remains elusive. Using a combination of extraoperative macro- and micro-electrode interictal recordings in presurgical patients we found that fast ripples (FR; 200-600Hz) frequently occur <300 msec before an interictal intracranial EEG (iEEG) spike. Such FR events are associated with higher spectral power, correlated with more vigorous neuronal firing than solitary FR. By contrast, during the iEEG spike that follows a FR, action potential firing is lower than during a iEEG spike alone. Sites containing a high proportion of FR preceding iEEG spikes correlate with brain areas where seizures begin. Despite this correlation, removal of these sites does not guarantee seizure freedom. These results are consistent with the hypothesis that FR preceding EEG spikes reflect an increase in local excitability that primes EEG spike discharges preferentially in the seizure onset zone and that epileptogenic brain regions are necessary, but not sufficient, for initiating interictal epileptiform discharges.

Competing Interest Statement

M.R.S has received compensation for speaking at continuing medical education (CME) programs from Medscape, Projects for Knowledge, International Medical Press, and Eisai. He has consulted for Medtronic, Neurelis, and Johnson & Johnson. He has received research support from Eisai, Medtronic, Neurelis, SK Life Science, Takeda, Xenon, Cerevel, UCB Pharma, Janssen, and Engage Pharmaceuticals. He has received royalties from Oxford University Press and Cambridge University Press. The remainder of the authors declare no competing interests.

Funding Statement

K23 NS094633 a Junior Investigator Award from the American Epilepsy Society R01 NS106958 R01 NS033310 European Research Council ERC-2019-CoG 864353 We would also like to thank Christina Louise George Trust and the Resnick Family Foundation.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

University of California Los Angeles Institutional Review Board Thomas Jefferson University Institutional Review Board

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

The data and code to reproduce the results and figures are available at https://zenodo.org/record/7685943#.Y_5UHybML9Z and https://github.com/shenweiss/FRexcitabilityprespike. The raw data is available upon reasonable request.

https://zenodo.org/record/7685943#.Y_5UHybML9Z

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