Glissandi: Transient fast electrocorticographic oscillations of steadily increasing frequency, explained by temporally increasing gap junction conductance

Abstract

Purpose: We describe a form of very fast oscillation (VFO) in patient electrocorticography (ECoG) recordings, that can occur prior to ictal events, in which the frequency increases steadily from ∼30-40 to >120 Hz, over a period of seconds. We dub these events "glissandi" and describe a possible model for them. Methods: Four patients with epilepsy had presurgical evaluations (with ECoG obtained in two of them), and excised tissue was studied in vitro, from three of the patients. Glissandi were seen spontaneously in vitro, associated with ictal events-using acute slices of rat neocortex-and they were simulated using a network model of 15,000 detailed layer V pyramidal neurons, coupled by gap junctions. Key findings: Glissandi were observed to arise from human temporal neocortex. In vitro, they lasted 0.2-4.1 s, prior to ictal onset. Similar events were observed in the rat in vitro in layer V of frontal neocortex when alkaline solution was pressure-ejected; glissandi persisted when γ-aminobutyric acid A (GABAA), GABAB, and N-methyl-d-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptors were blocked. Nonalkaline conditions prevented glissando generation. In network simulations it was found that steadily increasing gap junction conductance would lead to the observed steady increase in VFO field frequency. This occurred because increasing gap junction conductance shortened the time required for an action potential to cross from cell to cell. Significance: The in vitro and modeling data are consistent with the hypothesis that glissandi arise when pyramidal cell gap junction conductances rise over time, possibly as a result of an alkaline fluctuation in brain pH. © Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.