Limb coordination during locomotion before and after spinal cord injury

Georgia Institute Of Technology, Atlanta GA

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Abstract

Whether it is walking, playing sports/recreation, eating/drinking or mating, moving is essential to having a high quality of life. Traumatic spinal cord injury (SCI) is a catastrophic event that completely alters a person’s life, with a high cost to the health care system and the highest out-of-pocket expenses for individuals. Symptoms include weakened muscles, loss of sensation, and with the most severe injuries, complete motor paralysis. However, after SCI, the spinal sensorimotor circuits located below the injury remain largely intact and can be activated by pharmacology and/or electrical stimulation. Despite recent progress in restoring walking in people with SCI using electrical epidural stimulation of the lumbar cord, the restored gait is slow, uncoordinated, balance assistance is needed, and it lacks fluidity. Thus, it remains non-functional for community ambulation. A better understanding of spinal sensorimotor circuits and dynamic interactions between different locomotor control systems is required for successful treatment of SCI. Animal models have been instrumental in elucidating the sensorimotor circuits controlling locomotion and their contributions to functional recovery after SCI, and for developing therapeutic strategies, such as spinal electrical stimulation. A limitation of previous studies of locomotor recovery after SCI was that they mainly used thoracic SCI and analyzed two-dimensional kinematics during simple tasks, e.g. overground or treadmill locomotion on a flat surface. However, most SCIs in humans occur at cervical levels, and increasing locomotor task complexity recruits additional neural control mechanisms, rapidly revealing limitations to locomotor recovery after SCI. Thus, the proposed studies will expand investigations of spinal sensorimotor circuits and interactions between systems controlling limb coordination to cervical SCI and to natural overground environments requiring intact and spinal-injured cats to navigate complex terrains, make turns and step over obstacles. To interpret the experimental results and understand the interactions between spinal, supraspinal and somatosensory feedback mechanisms before and after SCI, we will extend our neuromechanical model to allow complex movements in three dimensions. The proposed studies will be performed in close interactive collaboration between two groups of investigators with strong and complementary expertise in experimental electrophysiological recordings and experimental and computational biomechanics of cat locomotion (Boris Prilutsky, Georgia Tech) and in computational neural control of locomotion (Ilya Rybak, Drexel University). The project has the following Specific Aims: (1) Determine organization of spinal sensorimotor circuits and interactions between systems controlling limb coordination during locomotion in three-dimensional space and (2) Determine changes in the neuromechanical control of intra- and interlimb coordination during locomotion after spinal cord injury at cervical-thoracic levels. Our results will have an important translational impact. We will continue building on our understanding of the control of limb coordination in health and disease. The framework provided by the model will identify neuromechanical mechanisms that we can specifically target to improve limb coordination in people with SCI and other movement disorders.