Spontaneous low-voltage fast limbic seizures in humans exhibit a specific excitatory-inhibitory imbalance at seizure onset.
Abstract number :
1.006
Submission category :
1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year :
2017
Submission ID :
348585
Source :
www.aesnet.org
Presentation date :
12/2/2017 5:02:24 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
Bahareh Elahian, Thomas Jefferson University; Nathan Lado, Thomas Jefferson University; Mohammed Yeasin, University of Memphis; Amrit Misra, Harvard University; Karen Moxon, University of California Davis; Itzhak Fried, UCLA; Ashwini D. Sharan, Thomas Jef
Rationale: Intracellular recordings during low-voltage fast (LVF) onset seizures from the entorhinal cortex in animal models of mesial-temporal lobe epilepsy have demonstrated that these seizures are initiated by a synchronous inhibitory event. We sought to determine if spontaneous limbic seizures in patients with medically refractory mesial-temporal lobe epilepsy also exhibited increased firing of inhibitory interneurons at onset. Methods: The seizure onset zone (SOZ) was identified using visual inspection of the intracranial EEG. We used wavelet clustering and temporal autocorrelations to characterize single unit activity in the local field potential (LFP) of microelectrode recordings from limbic structures before and during LVF activity during spontaneous human seizures. Putative excitatory and inhibitory single units were distinguished using K-mean clustering and features based on waveform morphology such as half width at half spike maximum (HWHM), peak amplitude asymmetry and trough to peak. Results: From a total of 102 implanted microelectrodes in five patients during seven LVF onset seizures we identified 104 single units. Of these 104 units 63.46% were located in the SOZ, and of these units 21.21% were classified as inhibitory. In the entorhinal cortex, hippocampus, and amygdala SOZ, inhibitory interneurons exhibited an increased firing rate prior to and during LVF seizure onset. During this epoch excitatory neuron firing decreased in the hippocampus. Following the increase in inhibitory neuron firing, excitatory neurons exhibited a rebound later during the LVF epoch in the entorhinal cortex, hippocampus, and amygdala. We found that the waveforms for both excitatory and inhibitory units remained stable during the LVF epoch (Mahalanobis value, p < 0.001) Conclusions: The results suggest that ictogenesis during spontaneous limbic seizures in humans with a LVF onset is also mediated by an increase in the firing rates of inhibitory interneurons. Funding: This work was supported by NIH/NINDS 5R01NS033310-23 (JE).Commonwealth Universal Research Enhancement (CURE) Program SAP #: 4100077067 (SAW)
Translational Research