Transcranial stimulation to enhance cortical plasticity in the healthy and stroke-affected motor system

This thesis investigated transcranial direct current stimulation (tDCS) as applied to the motor system, and its ability to modulate underlying cortical processes and resultant motor behaviours. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) were employed to assess the extent to which tDCS induces quantifiable changes in neural structure and function in controls and stroke patients. Modifications in the connectivity of intrinsic functional networks following tDCS application were examined using resting state fMRI. Polarity-specific changes were found: cathodal (inhibitory) tDCS increased the strength of the default mode network and increased functional coupling between major nodes within the motor network. No significant effects were found following anodal (excitatory) tDCS. Although anodal tDCS elicited only subtle changes in resting activity, it is known to produce robust modifications of behaviour. Single and paired-pulse TMS were used to investigate the neurophysiological underpinnings of these changes. Consistent with the theory of homeostatic plasticity, anodal tDCS applied prior to task performance increased GABAA-mediated cortical inhibition and worsened behaviour. The specificity of these changes suggests a central role for the mechanism of surround inhibition. A longitudinal clinical trial in chronic stroke patients was conducted to determine the utility of tDCS as an adjunct in motor rehabilitation. Serial MRI scans revealed that, when combined with motor training, anodal tDCS increased functional activity and grey matter in primarily ipsilesional motor areas. These brain changes were correlated with behavioural improvements in the stroke-affected upper limb. The laterality of connectivity at baseline, as measured by resting state activity and corticospinal tract integrity, was predictive of response to the rehabilitation program, particularly in those stroke patients who received tDCS. Asymmetry favouring the contralesional hemisphere predicted greater behavioural gains. Such results underscore the importance of re-normalisation of structure and functional activity toward the lesioned hemisphere in stroke rehabilitation.This thesis is not currently available in ORA