Dynamic Cortical Connectivity during General Anesthesia in Healthy Volunteers

Abstract

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Recent studies of anesthetic-induced unconsciousness in healthy volunteers have focused on functional brain connectivity patterns, but the protocols rarely parallel the depth and duration of surgical anesthesia. Furthermore, it is unknown whether there is a single functional connectivity pattern that correlates with general anesthesia for the duration of prolonged anesthetic exposure. Methods The authors analyzed electroencephalographic data in 30 healthy participants who underwent induction of anesthesia with propofol followed by 3 h of isoflurane anesthesia at age-adjusted 1.3 minimum alveolar concentration. Functional connectivity was assessed by frequency-resolved weighted phase lag index between frontal and parietal channels and between prefrontal and frontal channels, which were classified into a discrete set of states through k-means cluster analysis. Temporal dynamics were evaluated by the occurrence rate and dwell time distribution for each state as well as the transition probabilities between states. Results Burst suppression was present, with mean suppression ratio reducing from 44.8 ± 32.3% to 14.0 ± 20.2% (mean ± SD) during isoflurane anesthesia (P < 0.001). Aside from burst suppression, eight connectivity states were classified by optimizing the reproducibility of clustering solutions, with each characterized by distinct properties. The temporal progression of dominant states revealed a successive shifting trajectory from the state associated with alpha frontal-parietal connectivity to those associated with delta and alpha prefrontal-frontal connectivity during induction, which was reversed during emergence. Cortical connectivity was dynamic during maintenance period, and it was more probable to remain in the same state (82.0 ± 8.3%) than to switch to a different state (P < 0.001). However, transitions to other states were structured, i.e., occurred more frequently than expected by chance. Conclusions Anesthesia-induced alterations of functional connectivity are dynamic despite the stable and prolonged administration of isoflurane, in the absence of any noxious stimuli. Changes in connectivity over time will likely yield more information as a marker or mechanism of surgical anesthesia than any single pattern.

The Biology of General Anesthesia from Paramecium to Primate

“…These particular brain regions are important because they are posited to constitute a global neuronal workspace that is critical to consciousness [145], the impairment of which can account for traits of the anesthetized state [146]. However, recent studies have demonstrated that corticocortical functional connectivity shifts dynamically during exposure to volatile anesthetics, even when controlling for pharmacokinetic stability and surgical stimulus [147,148].…”

Alpha band frontal connectivity is a state-specific electroencephalographic correlate of unresponsiveness during exposure to dexmedetomidine and propofol

“…The analysis was focused on anterior and posterior areas (Fig 1), where anaesthetic-induced changes have been reported. 4e12 Another analysis was conducted within the anterior area, 6,8,13,14,17 which was evenly divided into prefrontal and frontal areas (Fig 1). The coherence, wPLI and dPLI values between prefrontal and frontal or between anterior and posterior regions were calculated for each pair of channels in the two regions and then averaged.…”

“…1e3 Reduced or even reversed anterioreposterior feedback connectivity has been considered as a neural correlate of unresponsiveness, 4e12 although recent evidence has suggested that anterioreposterior functional connectivity in the alpha band during general anaesthesia is not stable, but rather fluctuates dynamically and non-randomly over time. 13,14 In terms of local connectivity within the anterior area, both dexmedetomidine and propofol induce frontal coherence in broad alpha band, 1,15,16 and increased frontal-to-prefrontal connectivity within the alphaebeta frequency band has been reported in moderate and deep propofol sedation. 17 Regardless of these converging findings on frontal alpha activity, which have been further corroborated by fMRI studies that showed changes in the activation and connectivity of the frontal lobe in response to anaesthetics, 18e20 connected consciousness can occur despite the presence of a prominent frontal alpha-delta EEG pattern during surgical anaesthesia.…”

Syncopated Tempi of the Anesthetized Brain

“…I n this issue of Anesthesiology, there are two articles looking at changes in patterns of connectivity between different brain regions during general anesthesia. 1,2 These articles are full of the technical language of dynamics that might be somewhat daunting for clinicians. Can we make terms like "metastability," "spatiotemporal invariance," and even "connectivity" less abstract and more relevant to our day-today work?…”