Upper extremity motor impairments resulting from the neural damage caused by a stroke are often the focus of rehabilitation efforts. Research has demonstrated the plastic potential of the brain to change and reorganize following neurologic injury leading to conceptual shifts in stroke rehabilitation. These shifts include implementing structured, intensive protocols that are based on neurophysiologic, motor control, and motor learning principles to promote use-dependent plasticity. The following investigation is in response to the call from several prominent reviews for research to address specific mechanism based questions to advance stroke rehabilitation. Experiments were conducted to address two aims:​ the first aim was to determine how reaching task structure influences motor control strategies in survivors of stroke;​ and the second aim was to determine the effects of non-invasive motor cortex stimulation triggered by voluntary muscle activation to promote use dependent plasticity. Collectively, these studies provide a comprehensive investigation of how certain characteristics of interventions (e.g., the structure of the task) can influence motor control and neurophysiological outcomes in survivors of stroke. The first aim was accomplished with kinematic motion analysis methods to determine how reaching movement patterns were generated by survivors of stroke, and if differences occurred when reaching discretely versus cyclically. The majority of the survivors of stroke in this study were able to maintain continuous, cyclic motion without dwelling periods between movements. The results demonstrated that survivors of stroke use a distinct movement pattern during cyclic reaching compared to when performing discrete reaching, i.e., significantly more trunk rotation. We further determined that muscle activation patterns were generally less in the stroke-affected side for muscles in the shoulder girdle (e.g., anterior and posterior deltoid). These results suggest that the incorporation of cyclic reaching tasks may be an important aspect of interventions and assessments because it requires the continuous integration of afferent feedback with the efferent (motor) output to sustain goal-directed reaching. The second aim was to investigate the impact of a novel motor cortex stimulation paradigm, termed functional-rTMS, on motor control and neurophysiologic measures. During functional-rTMS, subjects were required to actively trigger each train of stimulation by sufficiently generating muscle activity in a lateral pinch task. We found that subjects responded differently to functional-rTMS compared to passive-rTMS, i.e., stimulation delivered while subjects were relaxed. Following functional-rTMS, subjects had less inhibition and more facilitation of neural networks in the primary motor cortex. We also observed a differential effect of functional-rTMS on muscle representations such that the agonist was preferentially modulated. The results of this study provide initial support for the potential to use functional-rTMS to modulate specific muscle groups within the same representation for survivors of stroke who often experience imbalances in flexion and extension in the upper extremity. Taken together, this collection of studies informs clinical researchers of a number of important mechanisms that can be incorporated into upper extremity stroke rehabilitation. Subjects who would likely qualify for intensive interventions are able to generate cyclic reaching without effects on motor performance. Incorporating such tasks within clinical interventions provides a learning opportunity to incorporate afferent feedback with efferent/motor output while completing repetitions. Secondly, functional-rTMS should be further explored with specific attention to the potential benefits of the differential effects on agonist versus antagonist muscle groups.