Low-voltage fast seizures in humans begin with increased interneuron firing.

Authors

• Bahareh Elahian
• Nathan E Lado
• Emily Mankin
• Sitaram Vangala
• Amrit Misra
• Karen Moxon
• Itzhak Fried
• Ashwini Sharan
• Mohammed Yeasin
• Richard Staba
• Anatol Bragin
• Massimo Avoli
• Michael R Sperling
• Jerome Engel
• Shennan A Weiss

Publication/Presentation Date

10-1-2018

Abstract

OBJECTIVE: Intracellular recordings from cells in entorhinal cortex tissue slices show that low-voltage fast (LVF) onset seizures are generated by inhibitory events. Here, we determined whether increased firing of interneurons occurs at the onset of spontaneous mesial-temporal LVF seizures recorded in patients.

METHODS: The seizure onset zone (SOZ) was identified using visual inspection of the intracranial electroencephalogram. We used wavelet clustering and temporal autocorrelations to characterize changes in single-unit activity during the onset of LVF seizures recorded from microelectrodes in mesial-temporal structures. Action potentials generated by principal neurons and interneurons (ie, putative excitatory and inhibitory neurons) were distinguished using waveform morphology and K-means clustering.

RESULTS: From a total of 200 implanted microelectrodes in 9 patients during 13 seizures, we isolated 202 single units; 140 (69.3%) of these units were located in the SOZ, and 40 (28.57%) of them were classified as inhibitory. The waveforms of both excitatory and inhibitory units remained stable during the LVF epoch (p > > 0.05). In the mesial-temporal SOZ, inhibitory interneurons increased their firing rate during LVF seizure onset (p <  0.01). Excitatory neuron firing rates peaked 10 seconds after the inhibitory neurons (p <  0.01). During LVF spread to the contralateral mesial temporal lobe, an increase in inhibitory neuron firing rate was also observed (p <  0.01).

INTERPRETATION: Our results suggest that seizure generation and spread during spontaneous mesial-temporal LVF onset events in humans may result from increased inhibitory neuron firing that spawns a subsequent increase in excitatory neuron firing and seizure evolution. Ann Neurol 2018;84:588-600.

Volume

84

Issue

4

First Page

588

Last Page

600

ISSN

1531-8249

Published In/Presented At

Elahian, B., Lado, N. E., Mankin, E., Vangala, S., Misra, A., Moxon, K., Fried, I., Sharan, A., Yeasin, M., Staba, R., Bragin, A., Avoli, M., Sperling, M. R., Engel, J., Jr, & Weiss, S. A. (2018). Low-voltage fast seizures in humans begin with increased interneuron firing. Annals of neurology, 84(4), 588–600. https://doi.org/10.1002/ana.25325

Disciplines

Medicine and Health Sciences

PubMedID

30179277

Department(s)

Department of Medicine

Document Type

Article