Separating the contributions of descending pathways to movement

Abstract

The corticospinal tract is well established as the dominant descending pathway in primates; however, it does not occupy an exclusive position in its ability to control movement. By lesioning this pathway, Lawrence and Kuypers (1968) demonstrated that a wide range of movements could be mediated by brainstem motor pathways, such as the reticulospinal tract. Fifty years after these experiments, the relative contributions of corticospinal and reticulospinal pathways to movement is still a topic of debate. Animal studies are invaluable in addressing this question and advancing our understanding of the motor system. However, these must be considered in combination with the use of non-invasive techniques in order to translate our findings into humans. This thesis describes three separate experiments. In the first, the mechanisms underlying transcranial magnetic stimulation (TMS) were investigated by applying TMS to anaesthetised rhesus macaques whilst recordings were made from individual corticospinal axons. Our results differ from the population effects observed in human recordings, emphasising the complexity of the responses evoked by TMS. Secondly, in humans we performed a choice reaction reaching task thought to involve tecto-reticulospinal pathways. By pairing stimuli targeting the reticular formation, we propose that the resulting change in muscle activity represents a modulation of reticulospinal output. Finally, a strength training study was performed in two rhesus macaques and the adaptations in corticospinal and reticulospinal pathways assessed, with EMG and spinal recordings implicating reticulospinal pathways in strength-induced adaptations. These experiments demonstrate that a comprehensive understanding of the motor system requires consideration of both the human and animal literature, with their respective strengths and limitations. Furthermore, we need to advance beyond the corticospinal-centric view that has dominated the field and instead consider the role of all neural elements in the motor system, including brainstem pathways and interneuron circuits. Only through such means can we further our clinical and scientific understanding of movement.