BOLD study of stimulation-induced neural activity and resting-state connectivity in medetomidine-sedated rat

Functional magnetic resonance imaging (fMRI) in anesthetized-animals is critical in studying the mechanisms of fMRI and investigating animal models of various diseases. Medetomidine was recently introduced for independent anesthesia for longitudinal (survival) fMRI studies in rats. Since stimulation-induced fMRI signal is anesthesia-dependent and its characteristics in rats under medetomidine are not fully elucidated, the blood oxygenation level dependent (BOLD) fMRI response to electrical forepaw stimulation under medetomidine was systematically investigated at 9.4 T. Robust activations in contralateral primary somatosensory cortex (SI) and thalamus were observed and peaked at the stimulus frequency of 9 Hz. The response in SI saturates at the stimulus strength of 4 mA while that in thalamus monotonically increases. In addition to fMRI data acquired with the forepaw stimulation, data were also acquired during the resting-state to investigate the synchronization of low frequency fluctuations (LFF) in the BOLD signal (<0.08 Hz) in different brain regions. LFF during resting-state have been observed to be synchronized between functionally related brain regions in human subjects while its origin is not fully understood. LFF have not been extensively studied or widely reported in anesthetized-animals. In our data, synchronized LFF of BOLD signals are found in clustered, bilaterally symmetric regions, including SI and caudate-putamen and the magnitude of the LFF is approximately 1.5%, comparable to the stimulation-induced BOLD signals. Similar to resting-state data reported in human subjects, LFF in rats under medetomidine likely reflect functional connectivity of these brain regions.