High-dose medetomidine increases functional connectivity in the fear-related regions after electrical stimulation

Anesthesia is essential, but not selective, in resting-state functional magnetic resonance imaging (fMRI) for pre-clinical studies. To mitigate stress and minimize head-movement artifacts, animals should be anesthetized during resting-state fMRI. Although the type, dosage, and timing of anesthesia can influence fMRI outcomes, responses to stimulation, and functional connectivity, the appropriate dosage of anesthesia is among the most important considerations. However, little is known about the effects of anesthetic dosage on innate fear responses induced by electrical stimulation. Therefore, we aimed to investigate the effects of medetomidine dosage on electrical stimulation and functional connectivity in fear-related regions. We conducted a graph-based network analysis of functional connectivity before and after electrical stimulation, based on different medetomidine dosages. We observed increased functional connectivity post-stimulation in the high-dose condition, but not in the low-dose condition. The high-dose condition showed increased global network properties post-stimulation compared to those observed pre-stimulation. In contrast, the low-dose condition showed no significant difference in global network properties between pre- and post-stimulation. The results suggest that high-dose medetomidine suppresses functional connectivity in fear-related regions in the brain; however, this suppressed functional connectivity can be recovered by electrical stimulation.