Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats

Abstract

Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology.Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats.Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection.Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.

Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents

“…The marmoset burst-suppression map is, to our knowledge, the first of its kind and suggests that V1 exclusion may be a general primate feature. The pancortical distribution of burst-suppression in rats agrees with all previous findings in this species, by fMRI (Aedo-Jury et al, 2020;Liu et al, 2013Liu et al, , 2011Paasonen et al, 2019;Schwalm et al, 2017) or calcium imaging (Ming et al, 2021). The strength of our approach lies in computing all maps with the same data-driven approach, thus allowing us to make direct cross-species comparisons.…”

“…The main inter-species difference was the exclusion of visual areas (and parts of other unimodal cortices) in primates, but not in rats. While bursts were traditionally viewed as synchronous cortexwide events, recent work rather describes them as complex waves (Bojak et al, 2015) emerging from a spatially shifting focus and rapidly spreading through the cortex (Ming et al, 2021). Electrocortical recordings in propofol-anesthetized human patients revealed that some electrodes could display continuous activity while others engaged in burst-suppression (Lewis et al, 2013).…”

“…Bursts have traditionally been viewed as globally synchronous events, based on their simultaneous occurrence across EEG electrodes (Clark and Rosner, 1973;Swank, 1949). However, recent findings from electrocorticogram in humans (Lewis et al, 2013) and widefield calcium imaging in rats (Ming et al, 2021), have challenged this view by demonstrating considerable spatial variation in burst origin and propagation. Furthermore, it is yet unclear whether burst-suppression is intrinsically cortical or is influenced by subcortical sources.…”

Instantaneous EEG Signal Analysis Based on Empirical Mode Decomposition Applied to Burst-Suppression in Propofol Anaesthesia

“…Examining the spectral content of recordings from different agents using EMD might prove fruitful in elucidating the differences between the mechanisms underlying different substances. Furthermore, localised presence of burst-suppression has been reported in the literature [32,33]. If different rhythms return at different rates, this might show up as e. g. changes in the origins for individual slow waves.…”

“…Изучение спектрального содержания ЭЭГ при применении различных препаратов с помощью РЭМ может оказаться полезным для выяснения различий между механизмами, лежащими в основе их действия. Кроме того, имеются сообщения о локализованном появлении ПВП [32,33]. Если различные ритмы вновь возникают на ЭЭГ после ПВП с разной скоростью, то это может проявиться, например, в виде изменений происхождения ferent suppression durations for underlying neural generators of these spectral components.…”