Functional MRI of sensorimotor and visual networks in rat brain before and after deafferentation induced neuroplasticity

Peripheral nerve injury can result from injuries occurring to the forearm and hand after automobile, industrial, and home accidents. These injuries can be extremely debilitating and can involve complications including a loss of sensorimotor function. The rat brain is an excellent model for systems biology. The purpose of this study is to examine the brain response to peripheral nerve injury in a rat model using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and BOLD resting-state functional connectivity MRI (fcMRI). Providing proper anesthetic and physiological maintenance is a key to the success of any small animal fMRI. An improved protocol for extended fMRI/fcMRI experiments is developed and used in all experiments. Two rat brain systems (sensorimotor and visual) were identified using novel fMRI stimulus paradigms. The BOLD response to frequency of a flicker visual stimulus was investigated. A second-order differential equation was developed to model the BOLD response to flicker stimulus and solved numerically to arrive at region-specific response functions. The model was able to mimic the major features of the data and the regional differences between model and experiment were shown to be due to neuronal activity. fcMRI is the study of correlations between brain regions in BOLD low frequency fluctuations (LFFs). The technique of fcMRI was extended to the study of rat brain at rest. New methods for analysis of rat fcMRI data are presented. Digits from rat forepaws were electrically stimulated, and the cortical representation of each digit was determined by BOLD fMRI using 300 micron cubic voxels. A somatotopic map of the BOLD activation in the central cortical layers revealed discrimination of individual digits and was in good agreement with electrophysiological studies. The introduction of high resolution MRI (9.4T) to the study of fcMRI is unique to this work. Functional connectivities between the cortical representations of the individual digits were determined from correlations of BOLD LFFs. The hypothesis was tested that the limits of spatial resolution between BOLD fMRI and BOLD fcMRI are similar. The highest correlation coefficients were detected between adjacent digits on the same forepaw and the same digit on opposite forepaws. The four major nerves of the rat forelimb were manipulated and BOLD fMRI and fcMRI was performed. Both the acute (<4 hours) and sub-acute (2 week) stages of recovery were accessed. The hypothesis that loss of afferent input to the sensorimotor system will cause changes in the resting and activated brain networks was tested. The reorganization in the entire resting sensorimotor system was studied. This work was directed toward the development of new techniques and models for the study of peripheral nerve injury. Knowledge acquired and techniques used during this study, including the application of fcMRI to brain plasticity, can be utilized in the future in human clinical imaging.