| Summary: | A stroke can have devastating consequences for an individual's gait and mobility, and difficulties often continue well after discharge from rehabilitation. Increased knowledge about the role of neural plasticity in stroke recovery has led to the development of neuromodulatory interventions. Neuromodulatory interventions can increase neural activity in the ipsilesional primary motor cortex and have potential to be used as rehabilitation adjuncts to facilitate recovery following stroke. This thesis explores a novel neuromodulatory intervention, thought to have neurophysiological underpinnings similar to that of paired associative stimulation (PAS), and is here called novel paired associative stimulation (novel PAS). Novel-PAS pairs the movement-related cortical potential (MRCP), recorded during imagined or voluntary movement, with peripheral electrical stimulation over a nerve supplying the target muscle. Novel-PAS can increase corticomotor excitability in the target muscle in healthy people. In people with stroke, a single study has shown increased corticomotor excitability for up to 30 minutes post-intervention, and improvements in lower limb impairment and function after three sessions targeting the ankle dorsiflexor muscles. Previous research has not considered how novel-PAS could best be implemented in rehabilitation, or assessed its feasibility when applied over several weeks. The aim of this thesis was to address gaps in the novel-PAS knowledge base. Specifically, this research investigates: the efficacy of novel-PAS beyond 30-minutes post intervention, the immediate effects of novel-PAS in people with stroke, and the feasibility of delivering a four week intervention. Study A, a within-subject, repeated-measures experiment in healthy people, explored the immediate effects of novel-PAS, and demonstrated increased corticomotor excitability to the tibialis anterior muscle for 60 minutes post-intervention. The findings provide new understanding about the duration of neuromodulatory effects following novel-PAS, knowledge that can guide decisions about the timing of the intervention within a standard rehabilitation session. Study B, a pilot randomised controlled trial in people with chronic stroke, evaluated the feasibility of a four-week novel-PAS intervention and research protocol. The protocol was not feasible for further research; the main barriers to its feasibility were the time requirements of the study and the use of transcranial magnetic stimulation (TMS) as an outcome measure. Recommendations are made to guide the development of future research protocols. New insights into the technical challenges of delivering novel-PAS, and potential limitations to its acceptability in the stroke population, are offered. Important recommendations are made for optimising the novel-PAS intervention to maximise its potential for implementation into rehabilitation practice. Study C, a repeated-measures, cross-over experiment in people with stroke, arose out of the need to investigate the within-session effects of novel-PAS, without using TMS-induced measures of corticomotor excitability. This study demonstrated that the novel-PAS intervention can significantly increase voluntary activation of the tibialis anterior muscle in people with chronic stroke. This provides important confirmation of the effects of novel PAS on neural plasticity and supports its potential to be used as a rehabilitation adjunct for people with stroke. Future research should focus on combining novel-PAS with standard rehabilitation techniques, assessing its cumulative effects on stroke recovery, and miniaturising the equipment.
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