Fast Ripples Reflect Increased Excitability That Primes Epileptiform Spikes
Abstract number :
1.026
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2023
Submission ID :
18
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Shennan Weiss, MD, PhD, FAES – SUNY Downstate
Jerome Engel, MD, PhD – Professor, UCLA; Itzhak Fried, MD PhD – Professor, UCLA; Michael Sperling, MD – Professor, Thomas Jefferson University; Robert Wong, PhD – Professor, SUNY Downstate; Yuval Nir, PhD – Tel Aviv University; Richard Staba, PhD – Professor, UCLA
Rationale: The neuronal circuit disturbances that drive interictal and ictal epileptiform discharges remains elusive.
Methods: We analyzed a combination of extraoperative macro and micro electrode interictal recordings in six presurgical patients during non-rapid eye movement sleep, and macroelectrode recordings in another 23 patients that underwent resections.
Results: We found that, exclusively in the seizure onset zone, fast ripples (FR; 200-600Hz), but not ripples (80-200 Hz), frequently occur < 300 msec before an interictal intracranial EEG (iEEG) spike with a probability exceeding chance (bootstrapping, p< 1e-5). Such FR events are associated with higher spectral power (p< 1e-10) and correlated with more vigorous neuronal firing than solitary FR (generalized linear mixed-effects model, GLMM, p< 1e-3) irrespective of FR power. During the iEEG spike that follows a FR, action potential firing is lower than during an iEEG spike alone (GLMM, p< 1e-10) reflecting an inhibitory restraint of iEEG spike initiation. In contrast, ripples do not appear to prime epileptiform spikes. We next investigated the clinical significance of pre-spike FR, sites containing a high proportion of FR preceding iEEG spikes correlated with brain areas where seizures begin more than solitary FR (p< 1e-5). Despite this correlation, removal of these sites does not guarantee seizure freedom.
Conclusions: 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.
Funding: This work was fully supported by the National Institute of Health K23 NS094633, a Junior Investigator Award from the American Epilepsy Society (S.A.W.), R01 NS106958 (R.J.S.) and R01 NS033310 (J.E.), European Research Council ERC-2019-CoG 864353 (Y·N.). The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the U.S. Government or the American Epilepsy Society.
Basic Mechanisms