A Study of Rodent Brain Function with Functional and Pharmacological Magnetic Resonance Imaging Joanna Huttunen A Study of Rodent Brain Function with Functional and Pharmacological Magnetic Resonance Imaging

It has been known for more than a century that stimulus induced neuronal activation evokes changes in the vascular system. During neuronal activation, the blood flow increase exceeds blood demand, and the amount of deoxygenated hemoglobin becomes reduced. Since deoxyhemoglobin is paramagnetic, this leads to an increased signal detectable with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). The aim of this study was to measure frequency modulated neural responses in the rat somatosensory cortex under the influence of two different anesthetic agents. Simultaneously recorded neural and BOLD responses differed under urethane and alphachloralose anesthesia but a linear relationship between neural response and BOLD was detected that was not dependent of the anesthetic used. Based on this study, the electrical stimulus parameters need to be optimized for each anesthetic to achieve optimal neural and hemodynamic responses. During a relatively long electrical stimulation, spontaneous fluctuations can occur in neuronal excitability. Temporal variations in BOLD responses were evaluated by a model based on the simultaneously measured neuronal local field potential (LFP) data and compared with the stimulus paradigm-based block model. Both LFP and block models alone had sufficient explanatory power to localize the activation to the somatosensory cortex of the rat. However, in comparison of these models, it was found that the LFP model was able to explain additional variation in the somatosensory BOLD signal over the block model. This indicates that there are temporal variations in the time-dependent changes in both neuronal and BOLD activation and the neurovascular coupling is preserved. Pharmacological magnetic resonance imaging (phMRI) is a novel fMRI application where the activation in the brain is evoked by a pharmacological agent. The possible fluctuations (e.g. room temperature, hardware drifts) in the BOLD time series that occurred in the time scale of the pharmacological activation may be difficult to filter, but could be eliminated by calculating T2 maps. The potent brain stimulant, nicotine and a weaker stimulant, apomorphine, were used in this study as test compounds to demonstrate the feasibility of using T2 map based approach to study quantitatively pharmacological activation. Functional and pharmacological magnetic resonance imaging in the preclinical setting offers an extensive array of possibilities with which to measure brain activity and when combined with direct invasive neuronal activity recordings, it represents an ideal way to deepen our understanding of the mechanisms of the physiological basis of the fMRI signals. The studies presented here have implications for both understanding brain function and for designing functional imaging paradigms in anesthetized animals. National Library of Medical Classification: QV 137, QV 771, QY 58, QY 60.R6, WB 330, WL 102, WL 141.5. M2 Medical Subject Headings: Anesthetics, General; Apomorphine; Electrical Stimulation; Electrodes, Implanted; Electroencephalography; Evoked Potentials, Somatosensory; Magnetic Resonance Imaging; Nicotine; Rats; Somatosensory cortex