Contributions of the Reticulospinal System to Movement Control and Functional Recovery in Patients With Spinal Cord Injury

Accurate movement execution is a result of a complex interplay between various muscle groups whose activity is controlled by different areas of the central nervous system. Besides the corticospinal system, the phylogenetically old reticulospinal system is a key motor system controlling different elementary movements including posture, locomotion and reaching across all mammals. In contrast to the extensively investigated corticospinal system, there is only sparse knowledge on the motor physiology of the functionally important reticulospinal system in humans. Reticulospinal motor control can be assessed with the StartReact paradigm which is based on the activation of reticulospinal motor circuitries by startling acoustic stimuli. The StartReact phenomenon is characterized by a shortening in movement reaction time which is mediated by a startle-triggered, early release of a planned motor program by the reticulospinal system. Thus, StartReact is a unique tool to examine reticulospinal involvement on human motor control under physiological and pathological conditions. StartReact assessments will be supplemented by comprehensive 3-D kinematic analysis and muscle activity recordings (i.e. electromyography) to gain quantitative insights into reticulospinal movement control.

The first objective of this clinical study is to gain more insights into the mechanisms underlying StartReact and to advance the knowledge on reticulo-spinal motor physiology regarding different movement tasks (i.e. simple single-joint movements, complex multi-joint movements and bilateral hand movements) in healthy subjects. The findings of these experiments will provide new insights into proximal-distal, flexor-extensor and upper-lower extremity gradients in reticulospinal motor control of healthy subjects. Moreover, the results will expand the StartReact paradigm to complex, functionally more relevant movements (i.e. reaching and stepping tasks requiring endpoint accuracy; co-operative, bilateral hand movements) for which the involvement of the reticulo-spinal system is not yet understood.

The second goal of this project is to use the StartReact paradigm to shed more light onto the role of reticulospinal plasticity in functional recovery of patients with spinal cord injury (SCI). Whereas preclinical findings emphasize a remarkable potential of the reticulospinal system for neuroplastic adaptations underlying functional recovery, there is only little evidence from clinical trials in the field of SCI. First, the study aims at monitoring StartReact effects in hand and leg muscles of patients with acute SCI over a period of 6 months. Simultaneous tracking of StartReact effects and motor recovery will allow to closely relate processes of reticulospinal plasticity to functional recovery in patients with acute SCI. Second, the focus will be on the re-weighting of descending motor control (i.e. cortico- vs. reticulospinal system) in response to SCI and investigate the distinct contributions of the cortico- and reticulospinal system to motor recovery in patients with chronic SCI.

The findings of this project will advance the mechanistic understanding on the motor physiology and neurorestorative capacity of the reticulospinal system in humans. New insights from these projects will hopefully translate into a better exploitation of this important motor system in clinical trials that aim to improve motor recovery in patients with SCI.