A Cumulative Refractoriness Accounts For The Reactive Behavior Of Anesthetic Burst-Suppression EEG Patterns

Calin A. (1), David B. (1), Constantinescu A.O. (1), Ilie A. (2), Nita D. (3), Zagrean A.-M. (1), Zagrean L. (1) & Moldovan M. (1,4) (1) Department of Physiology, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania; (2) Department of Pharmacology, Oxford University, Oxford, UK; (3) Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada; (4) Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

8th FENS Forum of Neuroscience, Barcelona
Presentation Code: p100.16 - Abstract Number: 3664 - Poster Board Number: B116 Abstract, Volume 6, p100.16, 2012
Session: P100: Oscillations and Synchrony I
Session Code: 100 Poster boards: B101-132
Date: Tuesday - July 17, 2012 11:15 - 13:15 (attendance: 11:15)
Theme/subtheme/subtopic: B. Excitability, synaptic transmission, network functions/ B.8 Network interactions/ B.8.b Oscillations and synchrony

At high concentrations of general anesthesia the EEG becomes discontinuous, consisting of bursts of activity lasting up to a few seconds that occur on a suppressed background, referred to as the burst-suppression (BS) pattern. With a further increase in anesthetic concentration there is a statistical decrease in bursting frequency (BF); however, stretches of high frequency bursts can still occur “spontaneously” or triggered by external stimulation. The mechanisms underlying this reactivity of BS patterns remain poorly understood. Recently, it was suggested that during the BS state various stimuli compete to generate bursts that spread rapidly over the whole cortex inducing a transient refractoriness during which the threshold for subsequent bust generation (TBG) is increased. We investigated the change in BF induced by visual stimuli or electrical nerve stimulation delivered at 2-second intervals during BS patterns induced by chloral hydrate or isoflurane in adult male Wistar rats. Although the BF remained increased for the whole duration of stimulation, the change in BF was higher at stimulus onset and then decreased to a plateau. The subsequent offset of stimulation was associated with a transient reduction in BF. This reactive behavior was independent of anesthetic and stimulus type used and could be reproduced in response to photic stimulation in sedated comatose patients. To model this behavior it was necessary and sufficient to consider that each burst caused a cumulative increase in TBG followed by an exponential recovery. Our data confirm previous observations of a burst-induced refractoriness and bring novel evidence that this refractoriness is cumulative. We propose that a cumulative cortical network disfacilitation is the principal mechanism limiting the BF during “spontaneous” and externally triggered BS patterns alike. Furthermore, this advances a simple explanation for the surprising bursting rhythmicity achieved occasionally during BS that fascinated generations of researchers.