Plasticity of interneuronal networks of the functionally isolated human spinal cord

Abstract

The loss of walking after human spinal cord injury has been attributed to the dominance of supraspinal over spinal mechanisms. The evidence for central pattern generation in humans is limited due to the inability to conclusively isolate the circuitry from descending and afferent input. However, studying individuals following spinal cord injury with no detectable influence on spinal networks from supraspinal centers can provide insight to their interaction with afferent input. The focus of this article is on the interaction of sensory input with human spinal networks in the generation of locomotor patterns. The functionally isolated human spinal cord has the capacity to generate locomotor patterns with appropriate afferent input. Locomotor Training is a rehabilitative strategy that has evolved from animal and humans studies focused on the neural plasticity of the spinal cord and has been successful for many people with acute and chronic incomplete spinal cord injury. However, even those individuals with clinically complete spinal cord injury that generate appropriate locomotor patterns during stepping with assistance on a treadmill with body weight support cannot sustain overground walking. This suggests that although a significant control of locomotion can occur at the level of spinal interneuronal networks the level of sustainable excitability of these circuits is still compromised. Future studies should focus on approaches to increase the central state of excitability and may include neural repair strategies, pharmacological interventions or epidural stimulation in combination with Locomotor Training. Capacity of functionally isolated human spinal cord to generate locomotor patternsThe loss of standing and walking after human spinal cord injury has been attributed to the dominance of supraspinal over spinal mechanisms in the control of locomotion in primates [34;57;84;106]. The evidence for central pattern generation in humans is limited due to the inability to conclusively isolate the circuitry from descending and afferent input [17-19;21; 41;60;68]. In studying the role of the human spinal cord in the generation of locomotor patterns we are restricted not only by our capacity to eliminate afferent input but also the ability to provide drugs or electrical stimulation directly to the spinal cord to activate the networks [10;62]. However, studying individuals following spinal cord injury with no detectable Susan Harkema, PhD, Frazier Rehab Institute, 220 Abraham Flexner Way, Louisville, KY 40202, susan.harkema@jhsmh.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal p...

Modular control of varied locomotor tasks in children with incomplete spinal cord injuries

“…During all locomotor tasks, he required nearly full assistance to complete the tasks. Based on these factors, his muscle activation during treadmill walking may reflect the influence of task-specific afferent input on spinal centers below his spinal cord lesion (Dietz and Harkema 2004;Harkema 2008;Maegele et al 2002). It is intriguing that some characteristics of this child's modular output were relatively consistent with healthy modular control, whereas some features were altered.…”

Facilitation of Postural Limb Reflexes With Epidural Stimulation in Spinal Rabbits

“…By contrast, stronger locomotor effects of EES were observed in chronic experiments, with the postlesion time from 2 wk to 2 mo . It is known that, at the later postlesion stages, significant plastic changes occur in the spinal cord, resulting in development of spasticity, which includes not only impairment of the system of spinal reflexes, but also augmentation of oscillatory properties of spinal neurons and thus instability of their networks (Harkema 2008;Ko et al 1999;Lyalka et al 2008). These dramatic changes in the functional state of the spinal networks toward the rhythmogenesis could be responsible for the changes in the effect of EES-from postural to locomotor ones.…”

“…It is well known that all spinal reflexes are subjected to considerable changes during the postlesion period, starting from their dramatic reduction during the initial phase of the spinal shock, which is followed by partial restoration and reorganization of the reflexes accompanied by the development of spasticity (Ditunno et al 2004;Harkema 2008;Ko et al 1999;Valero-Cabre et al 2004). One can therefore expect that the effects of EES also depend on time.…”

Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury

“…There is overwhelming evidence that the dramatic consequences of a severe SCI expand beyond these apparent deficits (Hiersemenzel et al, 2000;Dietz and Muller, 2004;Calancie et al, 2005;Courtine et al, 2009;Dietz et al, 2009;Boulenguez et al,electrophysiological studies have suggested that neuronal circuits deprived of supraspinal input undergo a progressive and extensive remodelling (Calancie et al, 1996(Calancie et al, , 2000Maegele et al, 2002;Beres-Jones et al, 2003;Calancie et al, 2005;Harkema, 2008); a process that continues to evolve for years after the SCI (Dietz, 2010). These alterations have been associated with the development of neuronal dysfunction in chronically paralysed individuals.…”