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Abstract
Stroke is a leading cause of disability with diverse sequelae. Motor impairment is the most common outcome post-stroke but is inherently heterogeneous and undergoes variable recovery. Despite the impact of such variability on patient assessment and rehabilitation, the clinical implications and underlying mechanisms remain poorly understood. Most clinical research focuses on homogeneous patient cohorts with mild to moderate impairment, while patients with low residual motor-function are under-represented. This thesis addresses motor heterogeneity in chronic stroke using multimodal behavioural, neurophysiological and neuroimaging techniques across a broad spectrum of motor impairment.
The first study utilised two novel therapy protocols to establish the retained capacity for improvement in chronic stroke, regardless of residual motor-function. The combination of bilateral priming and Wii-based Movement Therapy was effective particularly for those with low voluntary motor-function, and suggested that modulating cortical excitability may facilitate functional improvements. The remaining studies investigated mechanisms that may contribute to the capacity for improvement in chronic stroke. Transcranial magnetic stimulation revealed a complex inter-relationship between cortical excitability and motor-function, whereby no consistent pattern of altered excitability accompanied longitudinal improvements in motor-function. Physiological differences in the ipsilesional and contralesional hemispheres implicated both hemispheres in the processes of impairment and recovery after stroke. Patients with low motor-function emerged as physiologically distinct from those with higher function. Magnetoencephalography revealed novel patterns of brain activation whereby the amplitude and duration of movement-related cortical beta-oscillations were correlated with motor-function. Candidate-gene analysis demonstrated a novel interaction between BDNF genotype and residual motor-function. Finally, cross-modal analyses revealed a contrast between the prediction of motor status and therapy responsiveness in chronic stroke, suggesting that measures of white matter integrity can predict baseline function but not therapy gains.
The combined results of this thesis demonstrate the importance of patient stratification and the limitations of generalisation from homogeneous cohorts post-stroke. They emphasise the necessity of ongoing rehabilitation across the impairment spectrum and suggest that different mechanisms of recovery mediate improvement for patients of different residual motor capacities. These data provide evidence on which to base more balanced clinical trial design and more targeted and individualised therapy prescription after stroke.