Promoting use-dependent plasticity to improve upper limb recovery after stroke

Abstract

Motor recovery is a major factor influencing independence in everyday living after stroke. The objective of this dissertation was to explore two ways to promote use-dependent plasticity (UDP) to improve upper limb recovery after stroke. One approach was to adapt the delivery of training by incorporating auditory pacing. The specific aim was to augment UDP within the primary motor cortex (M1) by increasing synaptic efficacy through the synchronous arrival of auditory and sensorimotor input. Two cross-over, repeated-measures, studies were conducted in healthy adults. Training protocols consisted of simple, repetitive, upper limb movements that were either metronome-paced in synchrony or syncopation, selfpaced, or paced at a fast rate. Neurophysiological measures obtained with transcranial magnetic stimulation (TMS), and behavioural measures, were collected before and after training to evaluate UDP. The second approach was to prime M1 with theta burst stimulation (TBS) prior to training. The aim was to facilitate ipsilesional M1 excitability, and lower the threshold for UDP during subsequent training. TBS primed training was evaluated in two blinded, sham-controlled, repeated-measures studies in chronic subcortical stroke patients with upper limb impairment. In separate sessions, neurophysiological, behavioural, and clinical assessments were performed before and after precision grip training primed by one of three different TBS protocols (intermittent TBS, continuous TBS and sham TBS). A preliminary technical study was conducted to ensure the validity of the measure of sensorimotor integration used for the final study. Metronome-paced training at a comfortable speed improved synaptic efficacy within M1, as shown by selective facilitation of corticomotor excitability and altered kinematics of TMS-evoked movement that reflected the trained movement. Priming with intermittent TBS increased the receptiveness of ipsilesional M1 to afferent input and enabled stroke patients to engage in better quality motor training. Overall, this dissertation presents two clinically feasible approaches, “auditory-paced training” and “TBS primed training” to enhance UDP within a given therapy dose. Further clinical research is warranted to translate these promising novel approaches into rehabilitation practice.