Abstract

Abstract Background Reversible loss of consciousness is the primary therapeutic endpoint of general anesthesia; however, the drug‐invariant mechanisms underlying anesthetic‐induced unconsciousness are still unclear. This study aimed to investigate the static, dynamic, topological and organizational changes in functional brain network induced by five clinically‐used general anesthetics in the rat brain. Method Male Sprague–Dawley rats ( n = 57) were randomly allocated to received propofol, isoflurane, ketamine, dexmedetomidine, or combined isoflurane plus dexmedetomidine anesthesia. Resting‐state functional magnetic resonance images were acquired under general anesthesia and analyzed for changes in dynamic functional brain networks compared to the awake state. Results Different general anesthetics induced distinct patterns of functional connectivity inhibition within brain‐wide networks, resulting in multi‐level network reorganization primarily by impairing the functional connectivity of cortico‐subcortical networks as well as by reducing information transmission capacity, intrinsic connectivity, and network architecture stability of subcortical regions. Conversely, functional connectivity and topological properties were preserved within cortico‐cortical networks, albeit with fewer dynamic fluctuations under general anesthesia. Conclusions Our findings highlighted the effects of different general anesthetics on functional brain network reorganization, which might shed light on the drug‐invariant mechanism of anesthetic‐induced unconsciousness.