Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face

Abstract

Over the past 20 years, tremendous advances have been made in the field of spinal cord injury research. Yet, consumed with individual pieces of the puzzle, we have failed as a community to grasp the magnitude of the sum of our findings. Our current knowledge should allow us to improve the lives of patients suffering from spinal cord injury. Advances in multiple areas have provided tools for pursuing effective combination of strategies for recovering stepping and standing after a severe spinal cord injury. Muscle physiology research has provided insight into how to maintain functional muscle properties after a spinal cord injury.Understanding the role of the spinal networks in processing sensory information that is important for the generation of motor functions has focused research on developing treatments that sharpen the sensitivity of the locomotor circuitry and that carefully manage the presentation of proprioceptive and cutaneous stimuli to favor recovery. Pharmacological facilitation or inhibition of neurotransmitter systems, spinal cord stimulation, and rehabilitative motor training, which all function by modulating the physiological state of the spinal circuitry, have emerged as promising approaches. Early technological developments, such as robotic training systems and high-density electrode arrays for stimulating the spinal cord, can significantly enhance the precision and minimize the invasiveness of treatment after an injury.Strategies that seek out the complementary effects of combination treatments and that efficiently integrate relevant technical advances in bioengineering represent an untapped potential and are likely to have an immediate impact. Herein, we review key findings in each of these areas of research and present a unified vision for moving forward. Much work remains, but we already have the capability, and more importantly, the responsibility, to help spinal cord injury patients now. Keywordsspinal cord injury; rehabilitation; robotic motor training; pharmacological intervention; skeletal muscle adaptation; proprioception; epidural stimulation; locomotion Why does spinal cord injury result in a loss of movement control?Movements are defined by the combination of motor pools activated, the level at which they are recruited, and the effectiveness with which the corresponding muscles generate force. The diminished level of movement that follows a spinal cord injury has been attributed generally to an inability to activate motor pools. For most individuals with a spinal cord injury, however, this is less of a factor than typically assumed. Three more salient issues are linked to the impaired ability to recruit appropriate ensembles of motor units in a manner that yields effective movement. First, a significant portion of movement loss is attributable to functional alterations of the spinal circuitry that disrupt the coordination of the motor pools. Second, when a person with a severe, incomplete spinal cord lesion attempts to perform a movement, the level of recruitment is insuffi...

Electrocortical activity is coupled to gait cycle phase during treadmill walking

“…Spinal locomotor networks in humans and other vertebrates are capable of generating rhythmic muscle activity (Dietz, 2003;Dimitrijevic et al, 1998;Grillner, 1985;Rossignol, 2000;Rossignol et al, 2006;Shik and Orlovsky, 1976). However, activating this network in humans without functional descending motor pathways has proven to be difficult (Dietz et al, 1995;Ferris et al, 2004;Fong et al, 2009;Wirz et al, 2001). Some supraspinal locomotor centers are organized hierarchically in the brainstem, cerebellum, and cortex.…”

Noninvasive Reactivation of Motor Descending Control after Paralysis

“…[1][2][3] From the results of recent studies in mice and rats with motor complete paralysis we know that the lumbosacral spinal cord can be neuromodulated electrically and pharmacologically to enable motor control, including full weight-bearing stepping. 1,3,4 Recently we reported that four human patients having been motor complete for 2 or more years regained the ability to stand and voluntarily generate leg movements in the supine position with the aid of epidural stimulation. 5,6 Although the subjects were able to generate flexor movements with considerable precision, minimal locomotor-like movements were generated.…”

Facilitation of postural limb reflexes in spinal rabbits by serotonergic agonist administration, epidural electrical stimulation, and postural training

“…It is known that regular application of some factors, including training, electrical and pharmacological stimulation of the spinal cord, or their combination, results in restoration of locomotor functions in spinal animals (Antri et al 2003(Antri et al , 2005Courtine et al 2009;Edgerton et al 2008;Fong et al 2005Fong et al , 2009Gerasimenko et al 2008;Rossignol et al 2001). These findings suggest that such treatments prevent spontaneous changes in the isolated spinal network, leading to disintegration of locomotor central pattern generator, and induce plastic changes, resulting in the restoration of locomotor function.…”