Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats

2017 ◽  
Vol 23 (6) ◽  
pp. 664-680 ◽  
Author(s):  
Prithvi K. Shah ◽  
Igor Lavrov
Keyword(s):  
Motor Performance ◽  
Neural Circuitry ◽  
Clinical Implications ◽  
Pharmacological Agents ◽  
Epidural Stimulation ◽  
Cord Injury ◽  
Complete Spinal Cord Injury ◽  
Spinal Epidural ◽  
Stepping Response ◽  
Insight Into

Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful hindlimb stepping in spinal rats. Recent clinical and preclinical evidence indicates that motor training with ES plays a crucial role in tuning spinal neural circuitry to generate meaningful motor output. Concurrently administered pharmacology can also facilitate the circuitry to provide near optimal motor performance in SCI rats. However, as of today, the evidence for pharmacological agents to enhance motor function in persons with complete SCI is insignificant. These and other recent findings discussed in this review provide insight into addressing the translational gap, guide the design of relevant preclinical experiments, and facilitate development of new approaches for motor recovery in patients with complete SCIs.

scholarly journals Electrophysiological biomarkers of neuromodulatory strategies to recover motor function after spinal cord injury

2015 ◽  
Vol 113 (9) ◽  
pp. 3386-3396 ◽  
Author(s):  
Parag Gad ◽  
Roland R. Roy ◽  
Jaehoon Choe ◽  
Jack Creagmile ◽  
Hui Zhong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Evoked Potentials ◽  
Motor Performance ◽  
Weight Bearing ◽  
Chronic Administration ◽  
Pharmacological Agents ◽  
Extensor Muscles ◽  
Cord Injury ◽  
Complete Paralysis

The spinal cord contains the circuitry to control posture and locomotion after complete paralysis, and this circuitry can be enabled with epidural stimulation [electrical enabling motor control (eEmc)] and/or administration of pharmacological agents [pharmacological enabling motor control (fEmc)] when combined with motor training. We hypothesized that the characteristics of the spinally evoked potentials after chronic administration of both strychnine and quipazine under the influence of eEmc during standing and stepping can be used as biomarkers to predict successful motor performance. To test this hypothesis we trained rats to step bipedally for 7 wk after paralysis and characterized the motor potentials evoked in the soleus and tibialis anterior (TA) muscles with the rats in a non-weight-bearing position, standing and stepping. The middle responses (MRs) to spinally evoked stimuli were suppressed with either or both drugs when the rat was suspended, whereas the addition of either or both drugs resulted in an overall activation of the extensor muscles during stepping and/or standing and reduced the drag duration and cocontraction between the TA and soleus muscles during stepping. The administration of quipazine and strychnine in concert with eEmc and step training after injury resulted in larger-amplitude evoked potentials [MRs and late responses (LRs)] in flexors and extensors, with the LRs consisting of a more normal bursting pattern, i.e., randomly generated action potentials within the bursts. This pattern was linked to more successful standing and stepping. Thus it appears that selected features of the patterns of potentials evoked in specific muscles with stimulation can serve as effective biomarkers and predictors of motor performance.

scholarly journals Integrating multiple sensory systems to modulate neural networks controlling posture

2015 ◽  
Vol 114 (6) ◽  
pp. 3306-3314 ◽  
Author(s):  
I. Lavrov ◽  
Y. Gerasimenko ◽  
J. Burdick ◽  
H. Zhong ◽  
R. R. Roy ◽  
...  
Keyword(s):  
Neural Networks ◽  
Spinal Cord ◽  
Weight Bearing ◽  
Cumulative Effect ◽  
Epidural Stimulation ◽  
Lumbosacral Spinal Cord ◽  
Hindlimb Muscles ◽  
Neuronal Mechanisms ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

In this study we investigated the ability of sensory input to produce tonic responses in hindlimb muscles to facilitate standing in adult spinal rats and tested two hypotheses: 1) whether the spinal neural networks below a complete spinal cord transection can produce tonic reactions by activating different sensory inputs and 2) whether facilitation of tonic and rhythmic responses via activation of afferents and with spinal cord stimulation could engage similar neuronal mechanisms. We used a dynamically controlled platform to generate vibration during weight bearing, epidural stimulation (at spinal cord level S1), and/or tail pinching to determine the postural control responses that can be generated by the lumbosacral spinal cord. We observed that a combination of platform displacement, epidural stimulation, and tail pinching produces a cumulative effect that progressively enhances tonic responses in the hindlimbs. Tonic responses produced by epidural stimulation alone during standing were represented mainly by monosynaptic responses, whereas the combination of epidural stimulation and tail pinching during standing or epidural stimulation during stepping on a treadmill facilitated bilaterally both monosynaptic and polysynaptic responses. The results demonstrate that tonic muscle activity after complete spinal cord injury can be facilitated by activation of specific combinations of afferent inputs associated with load-bearing proprioception and cutaneous input in the presence of epidural stimulation and indicate that whether activation of tonic or rhythmic responses is generated depends on the specific combinations of sources and types of afferents activated in the hindlimb muscles.

Epidural stimulation for cardiovascular function increases lower limb lean mass in individuals with chronic motor complete spinal cord injury

2020 ◽  
Vol 105 (10) ◽  
pp. 1684-1691
Author(s):  
Bonnie Legg Ditterline ◽  
Susan J. Harkema ◽  
Andrea Willhite ◽  
Sean Stills ◽  
Beatrice Ugiliweneza ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lean Mass ◽  
Lower Limb ◽  
Cardiovascular Function ◽  
Epidural Stimulation ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

scholarly journals Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

2015 ◽  
Vol 114 (1) ◽  
pp. 400-410 ◽  
Author(s):  
Ursula S. Hofstoetter ◽  
Simon M. Danner ◽  
Brigitta Freundl ◽  
Heinrich Binder ◽  
Winfried Mayr ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Muscle Group ◽  
Lower Limbs ◽  
Spinal Reflex ◽  
Data Sets ◽  
Epidural Stimulation ◽  
Lumbosacral Spinal Cord ◽  
Cord Injury ◽  
Muscle Groups ◽  
Complete Spinal Cord Injury

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5–26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits.

scholarly journals Predictors of volitional motor recovery with epidural stimulation in individuals with chronic spinal cord injury

Brain ◽  
2020 ◽  
Author(s):  
Samineh Mesbah ◽  
Tyler Ball ◽  
Claudia Angeli ◽  
Enrico Rejc ◽  
Nicholas Dietz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lower Extremity ◽  
Lower Limb ◽  
Motor Recovery ◽  
Cervical Cord ◽  
Voluntary Movements ◽  
Epidural Stimulation ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Abstract Spinal cord epidural stimulation (scES) has enabled volitional lower extremity movements in individuals with chronic and clinically motor complete spinal cord injury and no clinically detectable brain influence. The aim of this study was to understand whether the individuals’ neuroanatomical characteristics or positioning of the scES electrode were important factors influencing the extent of initial recovery of lower limb voluntary movements in those with clinically motor complete paralysis. We hypothesized that there would be significant correlations between the number of joints moved during attempts with scES prior to any training interventions and the amount of cervical cord atrophy above the injury, length of post-traumatic myelomalacia and the amount of volume coverage of lumbosacral enlargement by the stimulation electrode array. The clinical and imaging records of 20 individuals with chronic and clinically motor complete spinal cord injury who underwent scES implantation were reviewed and analysed using MRI and X-ray integration, image segmentation and spinal cord volumetric reconstruction techniques. All individuals that participated in the scES study (n = 20) achieved, to some extent, lower extremity voluntary movements post scES implant and prior to any locomotor, voluntary movement or cardiovascular training. The correlation results showed that neither the cross-section area of spinal cord at C3 (n = 19, r = 0.33, P = 0.16) nor the length of severe myelomalacia (n = 18, r = −0.02, P = 0.93) correlated significantly with volitional lower limb movement ability. However, there was a significant, moderate correlation (n = 20, r = 0.59, P = 0.006) between the estimated percentage of the lumbosacral enlargement coverage by the paddle electrode as well as the position of the paddle relative to the maximal lumbosacral enlargement and the conus tip (n = 20, r = 0.50, P = 0.026) with the number of joints moved volitionally. These results suggest that greater coverage of the lumbosacral enlargement by scES may improve motor recovery prior to any training, possibly because of direct modulatory effects on the spinal networks that control lower extremity movements indicating the significant role of motor control at the level of the spinal cord.

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