Resting-state functional MRI as a tool for evaluating brain hemodynamic responsiveness to external stimuli in rats

PurposeAnesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting-state fMRI (rs-fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs-fMRI, such as functional connectivity (FC), are also directly related to blood-oxygen-level-dependent (BOLD) responses. MethodsA simple rs-fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1-hour interval. Supplementary forepaw stimulation experiments were also conducted. ResultsUnder thiobutabarbital anesthesia, FC was clearly coupled with nicotine-induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs-fMRI protocol revealed significant temporal changes in the FC in the -chloralose, thiobutabarbital, and urethane groups. ConclusionOur results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136-1146, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine