Increasing isoflurane dose reduces homotopic correlation and functional segregation of brain networks in mice as revealed by resting-state fMRI

Abstract

Effects of anesthetics on brain functional networks are not fully understood. In this work, we investigated functional brain networks derived from resting-state fMRI data obtained under different doses of isoflurane in mice using stationary and dynamic functional connectivity (dFC) analysis. Stationary network analysis using FSL Nets revealed a modular structure of functional networks, which could be segregated into a lateral cortical, an associative cortical network, elements of the prefrontal network, a subcortical network, and a thalamic network. Increasing isoflurane dose led to a loss of functional connectivity between the bilateral cortical regions. In addition, dFC analysis revealed a dominance of dynamic functional states (dFS) exhibiting modular structure in mice anesthetized with a low dose of isoflurane, while at high isoflurane levels dFS showing widespread unstructured correlation displayed highest weights. This indicates that spatial segregation across brain functional networks is lost with increasing dose of the anesthetic drug used. To what extent this indicates a state of deep anesthesia remains to be shown. Combining the results of stationary and dynamic FC analysis indicates that increasing isoflurane levels leads to loss of modular network organization, which includes loss of the strong bilateral interactions between homotopic brain areas.