Induction of plasticity in subcortical structures and its application in spinal cord injury

Abstract

Ph. D. ThesisMost current non-invasive plasticity protocols target the motor cortex and its corticospinal projections. Approaches for inducing plasticity in sub-cortical circuits and alternative descending pathways such as the reticulospinal tract (RST) are less well developed. The overall aim of this thesis was to gain a better understanding of the extent to which corticospinal transmissions are altered after spinal cord injury (SCI) and to explore the mechanisms of non-invasive stimulation protocols at the cortical and subcortical level. In the first study, transcranial magnetic stimulation was used to elicit motor-evoked potentials (MEPs) in the biceps brachii using different coil orientations, which allows for preferential activation of different neural elements. Analysis of MEP latencies suggests that differences between MEPs elicited by specific coil orientations may not be fully preserved in humans with cervical SCI, both in the biceps and in more distal muscle groups. In a second study, we developed a novel associative stimulation paradigm, which paired loud acoustic stimuli with transcranial magnetic stimulation over the motor cortex in healthy participants and observed enhanced motor output after stimulus pairing ended. Electrophysiological measurements in humans and direct measurements in monkeys undergoing a similar protocol implicate corticoreticular connections as the most likely substrate for the plastic changes. Finally, we used a custom built device to deliver precisely paired auditory clicks with electric stimulation to the muscle. We observed changes in electrophysiological measurements consistent with the induction of sub-cortical plasticity in the biceps muscle. We then used the same protocol to target the triceps muscle in individuals with SCI over the course of 4 weeks. Notably, we did not observe the same changes as in the biceps muscle, suggesting that elbow flexors and extensors have a different potential for plasticity, perhaps due to a differential control of flexor and extensor motoneurons by corticospinal and reticulospinal pathways.International Spinal Research Trus