Measuring motor-training induced neuroplasticity using diffusion and functional MRI: a sensitive, pathology-robust approach

Abstract

Brain injury constitutes a significant health burden worldwide, and outcomes are generally poor. To improve treatment, we must better understand how injury affects brain function, how the brain responds to learning pressures (neuroplasticity), and the interaction between the two. This is difficult, however, because of current technological shortcomings.This thesis focusses on the measurement of neuroplasticity in response to motor training in situations such as rehabilitation following brain injury. Although the principles and methods discussed generalise to many forms of brain pathology, discussion is generally focussed on unilateral cerebral palsy (UCP) because altered brain-development in UCP makes analyses particularly difficult. This begins with a literature review (Chapter 2) that outlines UCP, rehabilitative approaches, and the relationship between atypical brain organisation and early-life brain injury. Also discussed is how novel rehabilitation strategies may stem from studying brain changes induced by rehabilitation, and why the most informative findings are likely to come from studies utilising multiple imaging modalities.Blood Oxygen-Level Dependent Functional Magnetic Resonance Imaging (fMRI) measures brain activity indirectly and has been used to study neuroplasticity in both healthy participants and those with brain pathology. Although fMRI confounds are well understood, no published work has explored their cumulative effect when brain injury is present. Resultantly, confounds have largely been ignored, leading to heterogeneous findings that have provided little toward understanding brain changes, biologically speaking. Chapter 3 examines the cumulative effect of fMRI confounds, assumptions, and other issues, when attempting to measure neuroplasticity in participants with brain injury. This work concludes that, although fMRI can be expected to locate approximate regions of brain activation in an individual scan, numerous confounding factors make its interpretation, in terms of neuroplasticity, difficult without additional information acquired through alternative means.Diffusion MRI (dMRI) is an imaging modality that is typically used to identify the brain's white-matter pathways and calculate metrics that are influenced by factors such as myelination or axonal density. Standard dMRI analyses are ill suited to studying brain injury due to their reliance on brain 'atlases' which indicate relationships between brain regions and brain functions. Brain pathology can prevent reliable atlas registration, and alter relationships between structure and function. Chapter 4 details a novel dMRI analysis designed to measure neuroplasticity, addressing the need for a sensitive and reliable alternative to standalone-fMRI. This method utilises surface-based fMRI analyses, rather than brain atlases, to locate regions involved in motor execution. Corticospinal (CST) and thalamocortical tracts emanating from these regions are delineated using dMRI tractography and iii machine learning. This method was app...