Resting-state Dynamics as a Cortical Signature of Anesthesia in Monkeys

Abstract

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background The mechanism by which anesthetics induce a loss of consciousness remains a puzzling problem. We hypothesized that a cortical signature of anesthesia could be found in an increase in similarity between the matrix of resting-state functional correlations and the anatomical connectivity matrix of the brain, resulting in an increased function-structure similarity. Methods We acquired resting-state functional magnetic resonance images in macaque monkeys during wakefulness (n = 3) or anesthesia with propofol (n = 3), ketamine (n = 3), or sevoflurane (n = 3). We used the k-means algorithm to cluster dynamic resting-state data into independent functional brain states. For each condition, we performed a regression analysis to quantify function-structure similarity and the repertoire of functional brain states. Results Seven functional brain states were clustered and ranked according to their similarity to structural connectivity, with higher ranks corresponding to higher function-structure similarity and lower ranks corresponding to lower correlation between brain function and brain anatomy. Anesthesia shifted the brain state composition from a low rank (rounded rank [mean ± SD]) in the awake condition (awake rank = 4 [3.58 ± 1.03]) to high ranks in the different anesthetic conditions (ketamine rank = 6 [6.10 ± 0.32]; moderate propofol rank = 6 [6.15 ± 0.76]; deep propofol rank = 6 [6.16 ± 0.46]; moderate sevoflurane rank = 5 [5.10 ± 0.81]; deep sevoflurane rank = 6 [5.81 ± 1.11]; P < 0.0001). Conclusions Whatever the molecular mechanism, anesthesia led to a massive reconfiguration of the repertoire of functional brain states that became predominantly shaped by brain anatomy (high function-structure similarity), giving rise to a well-defined cortical signature of anesthesia-induced loss of consciousness.