Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury (original) (raw)
Related papers
Journal of Neurotrauma, 2016
Spinal cord epidural stimulation has resulted in the initiation of voluntary leg movements and improvement in postural, bladder, and sexual function. However, one of the limitations in reaching the full potential of epidural stimulation for therapeutic purposes in humans has been the identification of optimal stimulation configurations that can neuromodulate the spinal cord for stepping. In the present work, we investigated the mechanisms underlying the specificity of interaction between the rostral and caudal spinal cord circuitries in enabling locomotion in spinal rats (n = 10) by epidural spinal cord stimulation. By using unique spatiotemporal epidural stimulation parameters of the lumbar and sacral spinal cords, a robust stepping pattern in spinal rats was observed with only six training sessions and as early as 3 weeks post-injury. Electrophysiological evidence reveals that in addition to frequency of stimulation pulses at the stimulation sites, the relative timing between stimulation pulses applied at the lumbar (L2) and sacral (S1) segments of the spinal cord heavily impacted stepping performance. Best stepping was established at a higher stimulation frequency (40 Hz vs. 5, 10, 15, and 20Hz) and at specific relative time-intervals between the stimulation pulses (L2 pulse applied at 18-25 msec after the onset of the S1 pulse; S1 pulse applied 0-7 msec after the L2 pulse). Our data suggest that controlling pulse-to-pulse timing at multiple stimulation sources provides a novel strategy to optimize spinal stepping by fine-tuning the physiological state of the locomotor networks. These findings hold direct relevance to the clinician who will incorporate electrical stimulation strategies for optimizing control of locomotion after complete paralysis.
Neuromodulation of lower limb motor control in restorative neurology
Clinical Neurology and Neurosurgery, 2012
One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system.
Tapping into spinal circuits to restore motor function
Brain Research Reviews, 1999
Motivated by the challenge of improving neuroprosthetic devices, the authors review current knowledge relating to harnessing the potential of spinal neural circuits, such as reflexes and pattern generators. If such spinal interneuronal circuits could be activated, they could provide the coordinated control of many muscles that is so complex to implement with a device that aims to address each participating muscle individually. The authors' goal is to identify candidate spinal circuits and areas of research that might open opportunities to effect control of human limbs through electrical activation of such circuits. David McCrea's discussion of the ways in which hindlimb reflexes in the cat modify motor activity may help in developing optimal strategies for functional neuromuscular Ž . stimulation FNS , by using knowledge of how reflex actions can adapt to different conditions. Michael O'Donovan's discussion of the development of rhythmogenic networks in the chick embryo may provide clues to methods of generating rhythmic activity in the adult spinal cord. Serge Rossignol examines the spinal pattern generator for locomotion in cats, its trigger mechanisms, modulation and adaptation, and suggests how this knowledge can help guide therapeutic approaches in humans. Hugues Barbeau applies the work of Ž . Rossignol and others to locomotor training in human subjects who have suffered spinal cord injury SCI with incomplete motor function Ž . loss IMFL . Michel Lemay and Warren Grill discuss some of the technical challenges that must be addressed by engineers to implement a neuroprosthesis using electrical stimulation of the spinal cord, particularly the control issues that would have to be resolved. q
Nature Medicine, 2022
Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restored walking in people with spinal cord injury (SCI). However, EES was delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed a software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis, as part of an ongoing clinical trial (clinicaltrials.gov, NCT02936453). Within a single day, activity-specific stimulation programs enabled the three individuals to stand, walk, cycle, swim, and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.
Journal of Personalized Medicine
Spinal cord stimulation (SCS) is an approved treatment for intractable pain and has recently emerged as a promising area of research for restoring function after spinal cord lesion. This review will focus on the historical evolution of this transition and the path that remains to be taken for these methods to be rigorously evaluated for application in clinical practice. New developments in SCS are being driven by advances in the understanding of spinal cord lesions at the molecular, cellular, and neuronal levels, as well as the understanding of compensatory mechanisms. Advances in neuroengineering and the computational neurosciences have enabled the development of new conceptual SCS strategies, such as spatiotemporal neuromodulation, which allows spatially selective stimulation at precise time points during anticipated movement. It has also become increasingly clear that these methods are only effective when combined with intensive rehabilitation techniques, such as new task-oriente...
IFMBE Proceedings, 2009
In this report we shall review the finding that selective stimulation of tibial nerve large afferents and selective stimulation of lumbar sacral afferents to the spinal cord can elicit modification of motor output only by changing of the rate of the train of stimuli without changing the stimulus strength or site of stimulation. After a brief description of the applied methods in reported studies of suppression of sustained anti-clonus by train of stimuli of large afferents of tibial nerve at the sensory level, we shall point out that this "anti-clonus" effect depends from a particular frequency range. Other study in which we shall illustrate dependence from frequency rate of motor output it is epidural or transcutaneous stimulation of lumbar posterior roots; and how the frequency of applied stimulation trains can induce two completely different functional outputs of paralysed lower limbs (standing and locomotor-like movement) due to upper motor neuron lesion. At the end we shall discuss underlying mechanisms of this artificial "coding" in order to induce movement by afferent FES. Finally we shall discuss the significance of these findings for clinical practice of FES in upper motor neuron disorders.
Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury
eLife, 2018
Recovery from serious neurological injury requires substantial rewiring of neural circuits. Precisely-timed electrical stimulation could be used to restore corrective feedback mechanisms and promote adaptive plasticity after neurological insult, such as spinal cord injury (SCI) or stroke. This study provides the first evidence that closed-loop vagus nerve stimulation (CLV) based on the synaptic eligibility trace leads to dramatic recovery from the most common forms of SCI. The addition of CLV to rehabilitation promoted substantially more recovery of forelimb function compared to rehabilitation alone following chronic unilateral or bilateral cervical SCI in a rat model. Triggering stimulation on the most successful movements is critical to maximize recovery. CLV enhances recovery by strengthening synaptic connectivity from remaining motor networks to the grasping muscles in the forelimb. The benefits of CLV persist long after the end of stimulation because connectivity in critical neural circuits has been restored.
Brain, 2014
Previously, we reported that one individual who had a motor complete, but sensory incomplete spinal cord injury regained voluntary movement after 7 months of epidural stimulation and stand training. We presumed that the residual sensory pathways were critical in this recovery. However, we now report in three more individuals voluntary movement occurred with epidural stimulation immediately after implant even in two who were diagnosed with a motor and sensory complete lesion. We demonstrate that neuromodulating the spinal circuitry with epidural stimulation, enables completely paralysed individuals to process conceptual, auditory and visual input to regain relatively fine voluntary control of paralysed muscles. We show that neuromodulation of the sub-threshold motor state of excitability of the lumbosacral spinal networks was the key to recovery of intentional movement in four of four individuals diagnosed as having complete paralysis of the legs. We have uncovered a fundamentally new intervention strategy that can dramatically affect recovery of voluntary movement in individuals with complete paralysis even years after injury.