Learning induces functional and structural plasticity. This thesis used a range of neuroimaging approaches in both humans and rodents to address three main questions: (1) Can we predict learning performance using baseline imaging measures? (2) To what extent do performance outcomes or training amount determine experience-dependent plastic changes? (3) What biological mechanisms underlie white matter plasticity detected using MRI? Effects of performance and amount of practice on brain structure were studied by varying the amount of juggling practice. Brain structure was found to predict performance on a complex juggling task before learning acquisition. Both performance and practice were found to affect brain structure after learning. Overall, participants that achieved higher performances had higher grey matter (GM) and WM matter change. Also, participants that trained juggling for longer had higher positive brain changes than participants that practiced less. The effects of juggling performance and practice in functional connectivity and GABA levels as measured by MR spectroscopy (MRS) were also investigated. High intensity training was found to decrease the motor resting-state network strength while lower intensity increased the network strength. The increase in strength was associated with a decrease in GABA concentration. A correlation was also found between motor resting-state strength change and GABA concentration change after learning. Finally, since WM plasticity has not been thoroughly investigated and to understand which cellular events underlie WM change, an animal model of motor learning was combined with diffusion tensor imaging (DTI) and immunohistochemistry. Learning a novel motor task increased WM fractional anisotropy, an indirect measure of WM microstructure, in the contralateral hemisphere to the used paw. Immunohistochemistry staining with myelin basic protein (MBP) antibody of this region revealed higher myelin stain intensity for the learning group that correlated with performance in the task.