High Resolution Functional MRI Investigation of Cortical Plasticity Following Peripheral Nerve Injury and Repair

Recent clinical and laboratory studies have demonstrated that significant cortical plasticity appears following peripheral nerve injury and repair. Treatment based on cortical plasticity has been applied clinically to utilize this phenomenon and ensure the best possible outcome for these patients.;The ultimate goals of this proposal are to provide insight into the neural mechanism of cortical plasticity following peripheral nerve injury and repair, to monitor this cortical plasticity with high spatial resolution on a survival animal model, and eventually to develop a noninvasive method that can be used to guide clinical practice.;First, to better understand the neurophysiological mechanism of cortical plasticity following nerve injury and repair, high field functional MRI (fMRI) was employed to detect activation induced by direct nerve trunk electrical stimulation on the peripheral nervous system (PNS) in an animal model. Two distinct cortical plasticity patterns were demonstrated following different degrees of functional deprivation. Numerous studies have shown the critical role of cortical plasticity in the functional recovery process. Therefore, it is suggested that different degrees of functional loss caused by initial injury may lead to different types of cortical plasticity.;Second, to monitor functional recovery after peripheral nerve repair, a survival animal model was employed with simple median nerve injury and instant repair. Compared with the results of the previous non-survival animal model, the motor cortex blood oxygen level dependent (BOLD) activation disappeared during the scan. Further study may suggest that BOLD activation in the motor cortex may involve only a minimum level of consciousness. In this study, the same rats were studied over a prolonged period of time. Both fMRI and behavior tests were performed throughout the process. Significant correlations between the fMRI results and the behavior test results were found. This is the first time this relationship has been systematically studied, which would not have been possible without this new survival animal model. Using the same data set, resting state functional connectivity MRI (fcMRI) was also studied. A comparison between the nerve repair and non-repair groups yielded significant difference early in the subacute stage following initial injury. This technique could potentially be used to monitor nerve repair clinically to help patients with an extremely undesirable outcome. The entire sensory recovery process following nerve repair was also demonstrated using the fMRI technique for the first time. Meanwhile, fcMRI in the insular cortex was also investigated and remains consistent across different time points and independent from the cortical sensorimotor network. It may serve as a reliable control for any survival animal study.;Furthermore, to investigate cortical plasticity caused by PNS injury and repair and to apply the methodologies developed above, brachial plexus injury and repair in an animal model was studied. Cervical nerve root No. 7 autograph (C7 transfer) was used to repair the brachial plexus injury. By following the same rats for the entire recovery period, the process of cortical plasticity was revealed. For the first time, this process was demonstrated and studied quantitatively in great detail. Because individual rats could be followed over a long period of time, inter-subject variation was also investigated. Given the fact that the outcome of C7 transfer surgery shows great diversity clinically, this study provides a way to correlate individual surgical outcome with cortical reorganization. It also provides the basis for further intervention study to improve surgical outcome.;Finally, to maximize the detection abilities of both fMRI and fcMRI for future study, high resolution functional imaging was developed. We employed a half-k-space gradient echo (GE) sequence and pseudo-randomized digit stimulation. fMRI and fcMRI were performed at the cortical-column level. Results demonstrated fMRI BOLD activation; cortical-column activation was shown to penetrate the entire five layers of the cortex. The partial-volume effect was greatly reduced. A more accurate and localized result was demonstrated compared to results with a conventional resolution. This technique provides a solid foundation to investigate the PNS cortical-layer-specific projection of different fiber types in the future.