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Low‐voltage fast seizures in humans begin with increased interneuron firing
Author(s) -
Elahian Bahareh,
Lado Nathan E.,
Mankin Emily,
Vangala Sitaram,
Misra Amrit,
Moxon Karen,
Fried Itzhak,
Sharan Ashwini,
Yeasin Mohammed,
Staba Richard,
Bragin Anatol,
Avoli Massimo,
Sperling Michael R.,
Engel Jerome,
Weiss Shennan A.
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25325
Subject(s) - inhibitory postsynaptic potential , excitatory postsynaptic potential , neuroscience , interneuron , neuron , bursting , epilepsy , temporal lobe , entorhinal cortex , electrophysiology , biology , hippocampus , medicine , psychology
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