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.

Spatial specificity of cerebral blood volume-weighted fMRI responses at columnar resolution.

The spatial specificity of functional magnetic resonance imaging (fMRI) signals to columnar architecture remains uncertain. At columnar resolution, the specificity of intrinsic cerebral blood volume (CBV) response to orientation-selective columns in isoflurane-anesthetized cats was determined for CBV-weighted fMRI signals after injection of iron oxide at a dose of 10 mg Fe/kg. CBV-weighted fMRI data were acquired at 9.4 T with an in-plane resolution of 156 x 156 microm(2) in area 18 during visual stimulation at two orthogonal orientations. A 1-mm-thick imaging slice was selected tangential to the cortical surface. Regions with large CBV changes in response to two orthogonal orientation gratings were highly complementary. Maps of iso-orientation domains in response to these gratings were highly reproducible, suggesting that CBV-weighted fMRI has high sensitivity and specificity. The average distance between iso-orientation domains was 1.37+/- 0.28 mm (n=10 orientations) in an anterior-posterior direction. CBV-weighted fMRI signal change in the iso-orientation domains induced by preferred orientation was 1.69+/- 0.24 (n=10) times larger than that induced by orthogonal orientation. Our data demonstrate that CBV regulates at a submillimeter columnar scale and CBV-weighted fMRI has sufficient specificity to map columnar organization in animals.