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Background: After stroke, restoring safe, independent, and efficient walking is a top rehabilitation priority. However, in nearly 70% of stroke survivors asymmetrical walking patterns and reduced walking speed persist. This case series study aims to investigate the effectiveness of transcutaneous spinal cord stimulation (tSCS) in enhancing walking ability of persons with chronic stroke., Methods: Eight participants with hemiparesis after a single, chronic stroke were enrolled. Each participant was assigned to either the Stim group (N = 4, gait training + tSCS) or Control group (N = 4, gait training alone). Each participant in the Stim group was matched to a participant in the Control group based on age, time since stroke, and self-selected gait speed. For the Stim group, tSCS was delivered during gait training via electrodes placed on the skin between the spinous processes of C5-C6, T11-T12, and L1-L2. Both groups received 24 sessions of gait training over 8 weeks with a physical therapist providing verbal cueing for improved gait symmetry. Gait speed (measured from 10 m walk test), endurance (measured from 6 min walk test), spatiotemporal gait symmetries (step length and swing time), as well as the neurophysiological outcomes (muscle synergy, resting motor thresholds via spinal motor evoked responses) were collected without tSCS at baseline, completion, and 3 month follow-up., Results: All four Stim participants sustained spatiotemporal symmetry improvements at the 3 month follow-up (step length: 17.7%, swing time: 10.1%) compared to the Control group (step length: 1.1%, swing time 3.6%). Additionally, 3 of 4 Stim participants showed increased number of muscle synergies and/or lowered resting motor thresholds compared to the Control group., Conclusions: This study provides promising preliminary evidence that using tSCS as a therapeutic catalyst to gait training may increase the efficacy of gait rehabilitation in individuals with chronic stroke. Trial registration NCT03714282 (clinicaltrials.gov), registration date: 2018-10-18., (© 2024. The Author(s).)

Neuromodulation via spinal stimulation is a promising therapy that can augment the neuromuscular capacity for voluntary movements, standing, stepping, and posture in individuals with spinal cord injury (SCI). The spinal locomotor-related neuronal network known as a central pattern generator (CPG) can generate a stepping-like motor output in the absence of movement-related afferent signals from the limbs. Using epidural stimulation (EP) in conjunction with activity-based locomotor training (ABLT), the neural circuits can be neuromodulated to facilitate the recovery of locomotor functions in persons with SCI. Recently, transcutaneous spinal stimulation (scTS) has been developed as a noninvasive alternative to EP. Early studies of scTS at thoracolumbar, coccygeal, and cervical regions have demonstrated its effectiveness in producing voluntary leg movements, posture control, and independent standing and improving upper extremity function in adults with chronic SCI. In pediatric studies, the technology of spinal neuromodulation is not yet widespread. There are a limited number of publications reporting on the use of scTS in children and adolescents with either cerebral palsy, spina bifida, or SCI., Competing Interests: Conflicts of Interest Dr. Gerasimenko has a relationship with Cosyma, Ltd, Moscow Russia. He is a founder and Scientific Director of Cosyma and holds a patent on a stimulator used in research. He is funded by National Institutes of Health grant (R01 NS102920-01A1), the Craig H. Neilsen Foundation, and the Kentucky Spinal Cord and Head Injury Research Trust Fund. Dr. Behrman has received support from the Jewish Heritage Foundation for Excellence, National Center for Neuromodulation for Rehabilitation, Kentucky Spinal Cord and Head Injury Research Board, The Craig H. Neilsen Foundation, and Oxford University Press. Kosair Charities made payments to University of Louisville Foundation Inc., and Kosair Charities made payment directly to the institution from 2014-2016. Drs. Lucas and Singh received support from Kosair Charities (OGMB141540), National Center of Neuromodulation for Rehabilitation (NM4R) (CCDN190765), Kentucky Spinal Cord and Head Injury Research Board (OGMB210076), and the Jewish Heritage Foundation for Excellence (OGMN190574A). Dr. Martin received support from Orokawa Foundation, Niche Biomedical, and Kennedy Krieger Institute and research support to the Kennedy Krieger Institute., (©2023 American Spinal Injury Association.)

(1) Background: Restoring arm and hand function is a priority for individuals with cervical spinal cord injury (cSCI) for independence and quality of life. Transcutaneous spinal cord stimulation (tSCS) promotes the upper extremity (UE) motor function when applied at the cervical region. The aim of the study was to determine the effects of cervical tSCS, combined with an exoskeleton, on motor strength and functionality of UE in subjects with cSCI. (2) Methods: twenty-two subjects participated in the randomized mix of parallel-group and crossover clinical trial, consisting of an intervention group ( n = 15; tSCS exoskeleton) and a control group ( n = 14; exoskeleton). The assessment was carried out at baseline, after the last session, and two weeks after the last session. We assessed graded redefined assessment of strength, sensibility, and prehension (GRASSP), box and block test (BBT), spinal cord independence measure III (SCIM-III), maximal voluntary contraction (MVC), ASIA impairment scale (AIS), and WhoQol-Bref; (3) Results: GRASSP, BBT, SCIM III, cylindrical grip force and AIS motor score showed significant improvement in both groups ( p ≤ 0.05), however, it was significantly higher in the intervention group than the control group for GRASSP strength, and GRASSP prehension ability ( p ≤ 0.05); (4) Conclusion: our findings show potential advantages of the combination of cervical tSCS with an exoskeleton to optimize the outcome for UE.

Personality traits (PTs) are predictors of the success of control of brain-computer interfaces (BCIs); however, it is unknown how the PTs that are optimal for BCI control changes during training. The paper for the first time analyzes the correlations between PTs and the accuracy of the classification (AC) of brain states in imagining the movements of the hands, feet, and locomotion during 10-day training of ten volunteers in BCI control. In the first 3 days of training, the AC is higher for more stressed and anxious volunteers; in the last days, for calmer ones. In the middle of the training period, AC is higher in low-demonstrativeness persons, it is more pronounced when imagining foot movements. Correlations of low demonstrativeness, as well as of foresight and self-control with AC when imagining foot movements are revealed significantly more often than when imagining hand movements and locomotions. During almost the entire period of training, AC with locomotion imagination is higher in individualists. The results make it possible to propose individually-oriented recommendations for the use of BCI based on the imagination of movements for the rehabilitation of patients with motor disorders., (© 2022. Pleiades Publishing, Ltd.)

Neural networks in the spinal cord can generate the walking pattern and control posture in the absence of supraspinal influences. A technology using transcutaneous electrical spinal cord stimulation (tSCS) was created. During walking, tSCS activated spinal locomotor networks, as well as leg flexor/extensor motor pools in the swing/stance phases, respectively. It was assumed that the use of this technology in subjects with locomotion disorders would improve walking. Patients with hemiparesis were studied 3-11 months after stroke, the duration of the course was 2 weeks. Patients of the main and control groups received standard therapy and rehabilitation using the technology; in the control group, sham tSCS was used. After the course, minimal clinically important differences in walking parameters were achieved in the main group, in contrast to the control group. The developed technology is an effective means of restoring walking in patients with hemiparesis., (© 2022. Pleiades Publishing, Ltd.)

It has been suggested that neuroplasticity-promoting neuromodulation can restore sensory-motor pathways after spinal cord injury (SCI), reactivating the dormant locomotor neuronal circuitry. We introduce a neuro-rehabilitative approach that leverages locomotor training with multi-segmental spinal cord transcutaneous electrical stimulation (scTS). We hypothesized that scTS neuromodulates spinal networks, complementing the neuroplastic effects of locomotor training, result in a functional progression toward recovery of locomotion. We conducted a case-study to test this approach on a 27-year-old male classified as AIS A with chronic SCI. The training regimen included task-driven non-weight-bearing training (1 month) followed by weight-bearing training (2 months). Training was paired with multi-level continuous and phase-dependent scTS targeting function-specific motor pools. Results suggest a convergence of cross-lesional networks, improving kinematics during voluntary non-weight-bearing locomotor-like stepping. After weight-bearing training, coordination during stepping improved, suggesting an important role of afferent feedback in further improvement of voluntary control and reorganization of the sensory-motor brain-spinal connectome.

The use of transcutaneous electrical spinal stimulation (TSS) to modulate sensorimotor networks after neurological insult has garnered much attention from both researchers and clinicians in recent years. Although many different stimulation paradigms have been reported, the interlimb effects of these neuromodulation techniques have been little studied. The effects of multisite TSS on interlimb sensorimotor function are of particular interest in the context of neurorehabilitation, as these networks have been shown to be important for functional recovery after neurological insult. The present study utilized a condition-test paradigm to investigate the effects of interenlargement TSS on spinal motor excitability in both cervical and lumbosacral motor pools. Additionally, comparison was made between the conditioning effects of lumbosacral and cervical TSS and peripheral stimulation of the fibular nerve and ulnar nerve, respectively. In 16/16 supine, relaxed participants, facilitation of spinally evoked motor responses (sEMRs) in arm muscles was seen in response to lumbosacral TSS or fibular nerve stimulation, whereas facilitation of sEMRs in leg muscles was seen in response to cervical TSS or ulnar nerve stimulation. The decreased latency between TSS- and peripheral nerve-evoked conditioning implicates interlimb networks in the observed facilitation of motor output. The results demonstrate the ability of multisite TSS to engage interlimb networks, resulting in the bidirectional influence of cervical and lumbosacral motor output. The engagement of interlimb networks via TSS of the cervical and lumbosacral enlargements represents a feasible method for engaging spinal sensorimotor networks in clinical populations with compromised motor function. NEW & NOTEWORTHY Bidirectional interlimb modulation of spinal motor excitability can be evoked by transcutaneous spinal stimulation over the cervical and lumbosacral enlargements. Multisite transcutaneous spinal stimulation engages spinal sensorimotor networks thought to be important in the recovery of function after spinal cord injury.

Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes.

Brain-computer interfaces (BCIs), based on motor imagery, are increasingly used in neurorehabilitation. However, some people cannot control BCI, predictors of this are the features of brain activity and personality traits. It is not known whether the success of BCI control is related to interhemispheric asymmetry. The study was conducted on 44 BCI-naive subjects and included one BCI session, EEG-analysis, 16PF Cattell Questionnaire, estimation of latent left-handedness, and of subjective complexity of real and imagery movements. The success of brain states recognition during imagination of left hand (LH) movement compared to the rest is higher in reserved, practical, skeptical, and not very sociable individuals. Extraversion, liveliness, and dominance are significant for the imagination of right hand (RH) movements in "pure" right-handers, and sensitivity in latent left-handers. Subjective complexity of real LH and of imagery RH movements correlates with the success of brain states recognition in the imagination of movement of LH compared to RH and depends on the level of handedness. Thus, the level of handedness is the factor influencing the success of BCI control. The data are supposed to be connected with hemispheric differences in motor control, lateralization of dopamine, and may be important for rehabilitation of patients after a stroke.

Personality traits of users can affect the success in controlling brain-computer interfaces (BCIs), and the activity of right and left brain structures may differ depending on personality traits. Earlier, it was not known, how the success of BCI control with different personality traits is associated with interhemispheric asymmetry. In this work, the dependence of the success of imagination of movements, estimated by the success of recognition of EEG signals during imagination of hand movements compared to rest state, on the user's personal characteristics was studied. It is shown that in single control of BCI by naive subjects, recognition success in imagining right-hand (RH) movements was higher in expressive sensitive extroverts, and in imagining left-hand movements (LH) it was higher in practical, reserved, skeptical, and not very sociable persons. It is suggested that this phenomenon may be based on interhemispheric differences in dopamine level and in the way of encoding movement information.

Key Points: Epidural electrical stimulation (ES) of the spinal cord restores/improves locomotion in patients. ES-evoked locomotor movements differ to some extent from the normal ones. Operation of the locomotor network during ES is unknown. We compared the activity of individual spinal neurons during locomotion initiated by signals from the brainstem and by ES. We demonstrated that the spinal network generating locomotion under each of the two conditions is formed by the same neurons. A part of this network operates similarly under the two conditions, suggesting that it is essential for generation of locomotion under both conditions. Another part of this network operates differently under the two conditions, suggesting that it is responsible for differences in the movement kinematics observed under the two conditions., Abstract: Locomotion is a vital motor function for both animals and humans. Epidural electrical stimulation (ES) of the spinal cord is used to restore/improve locomotor movements in patients. However, operation of locomotor networks during ES has never been studied. Here we compared the activity of individual spinal neurons recorded in decerebrate cats of either sex during locomotion initiated by supraspinal commands (caused by stimulation of the mesencephalic locomotor region, MLR) and by ES. We found that under both conditions, the same neurons had modulation of their activity related to the locomotor rhythm, suggesting that the network generating locomotion under the two conditions is formed by the same neurons. About 40% of these neurons had stable modulation (i.e. small dispersion of their activity phase in sequential cycles), as well as a similar phase and shape of activity burst in MLR- and ES-evoked locomotor cycles. We suggest that these neurons form a part of the locomotor network that operates similarly under the two conditions, and are critical for generation of locomotion. About 23% of the modulated neurons had stable modulation only during MLR-evoked locomotion. We suggest that these neurons are responsible for some differences in kinematics of MLR- and ES-evoked locomotor movements. Finally, 25% of the modulated neurons had unstable modulation during both MLR- and ES-evoked locomotion. One can assume that these neurons contribute to maintenance of the excitability level of locomotor networks necessary for generation of stepping, or belong to postural networks, activated simultaneously with locomotor networks by both MLR stimulation and ES., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Objective: The importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans., Methods: Ulnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants., Results: Potentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones., Conclusions: Descending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation., Significance: Evaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation.., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Neuromodulation of spinal networks can improve motor control after spinal cord injury (SCI). The objectives of this study were to (1) determine whether individuals with chronic paralysis can stand with the aid of non-invasive electrical spinal stimulation with their knees and hips extended without trainer assistance, and (2) investigate whether postural control can be further improved following repeated sessions of stand training. Using a double-blind, balanced, within-subject cross-over, and sham-controlled study design, 15 individuals with SCI of various severity received transcutaneous electrical spinal stimulation to regain self-assisted standing. The primary outcomes included qualitative comparison of need of external assistance for knee and hip extension provided by trainers during standing without and in the presence of stimulation in the same participants, as well as quantitative measures, such as the level of knee assistance and amount of time spent standing without trainer assistance. None of the participants could stand unassisted without stimulation or in the presence of sham stimulation. With stimulation all participants could maintain upright standing with minimum and some ( n  = 7) without external assistance applied to the knees or hips, using their hands for upper body balance as needed. Quality of balance control was practice-dependent, and improved with subsequent training. During self-initiated body-weight displacements in standing enabled by spinal stimulation, high levels of leg muscle activity emerged, and depended on the amount of muscle loading. Our findings indicate that the lumbosacral spinal networks can be modulated transcutaneously using electrical spinal stimulation to facilitate self-assisted standing after chronic motor and sensory complete paralysis.

Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.

Changes in the blood flow in the shin skin were observed by laser Doppler flowmetry after transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz in 12 healthy subjects. It was found that TSCS in the area of the T 11 and L 1 vertebrae led to a significant increase in skin blood flow. The microcirculation rate increased by more than 85% relative to the baseline at a stimulus intensity of 90% of the motor threshold. Cutaneous blood flow activization by TSCS is implemented mainly through the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important mediator that contributes to vasodilation and increase in cutaneous blood flow upon TSCS. NO is predominantly of endothelial origin.

Background: Spinal cord injury causes significant impairments of both motor and pelvic organ functions. Latest studies have shown impressive potentials for using transcutaneous spinal cord electrical stimulation (TcSCES) in the late period of injury to restore motor functions. All results were obtained in a limited number of patients in the specific conditions of a physiological experiment. It remains unclear how effective a TcSCES cycle is in restoring motor activity in patients after spinal cord injury in real clinical conditions., Aim: The main objective of this investigation was to study the effectiveness of TcSCES in combination with the standard rehabilitation of patients after a spinal cord injury. An additional objective was to evaluate the effect of TcSCES to excretory functions in patients with spinal cord injury., Subjects and Methods: The studies were conducted at Saint Petersburg City Hospital Forty, which included 15 patients with thoracic spinal injury at 2.4±2.06 years after injury; the severity of the latter was American Spinal Injury Association (ASIA) Grades B and C. All the patients underwent a 2-week standard cycle of rehabilitation treatment; of them 7 patients (a study group) received additionally TcSCES. Standard scales were used to assess neurological status and muscle strength and sensitivity. The patients filled out a urinary diary; residual urine volume was monitored using bladder catheterization or ultrasound., Results: An increase in muscle strength was recorded in 6 patients of the study group and in 1 patient of the control one. The end of the treatment cycle was marked by a 1-score spasticity increase in 1 patient of the study group and in 2 patients in the control one. In the study group, the level of anesthesia decreased per segment in 1 patient; an improvement in deep and proprioceptive sensitivity was recorded in 2 patients; no change in sensitivity was observed in the control group. In the study group, 2 patients showed a reduction in the severity of injury from ASIA Grade B to ASIA Grade C. In three patients of the study group, the residual urine volume decreased and control and a sensation of urgency to urinate appeared; in the control group, these parameters remained unchanged after the treatment cycle., Discussion: The main result of the study is evidence for the efficiency of using TcSCES in the complex therapy of motor neurorehabilitation. The performed cycle of TcSCES in patients was noted to result in better motor and excretory functions., Conclusion: The use of a short-term TcSCES cycle in the motor rehabilitation program for patients with spinal cord injury contributes to recovery of severe motor disorders and is accompanied by an improvement in urinary functions.

As part of a project aimed to develop a novel, non-invasive techniques for comprehensive assessment of supraspinal-spinal connectivity in humans, the present study sought to explore the convergence of descending vestibulospinal and corticospinal pathways onto lumbosacral motor pools. Transcutaneous electrical spinal stimulation-evoked motor potentials were recorded from knee and ankle flexors and extensors in resting neurologically intact participants. Descending influences on lumbosacral motor neurons were studied using galvanic vestibular (GVS) or transcranial magnetic stimulation (TMS) to elicit descending vestibulospinal or corticospinal volleys, respectively. Facilitatory conditioning effects of descending corticospinal volleys were manifested by a significant increase of spinally evoked motor potentials in recorded knee and ankle muscles bilaterally, and were observed at the 10-30 ms conditioning-test intervals (CTIs); whereas, facilitatory conditioning effects of vestibulospinal volleys manifested at longer latencies (CTIs of 90 and 110 ms), and lasted up to 250 ms. TMS mediated volleys revealed the conditioning effects at both short and long latencies, suggestive of both direct and indirect influence. In contrast, vestibulospinally mediated conditioning effects occurred at longer latencies, consistent with this pathway's known anatomical and functional interfaces with other descending systems including the reticulospinal pathway and, suggestively, propriospinal interneurons. Our work demonstrates the utility and sensitivity of transcutaneous spinal stimulation in human neurophysiological studies as a technique for quantitative characterization of excitatory conditioning effects in multiple lumbosacral motor pools, obtained through descending pathways. This characterization becomes critical in understanding the neuroplasticity in the central nervous system during motor learning and neurological recovery.

Electrical neuromodulation of spinal networks improves the control of movement of the paralyzed limbs after spinal cord injury (SCI). However, the potential of noninvasive spinal stimulation to facilitate postural trunk control during sitting in humans with SCI has not been investigated. We hypothesized that transcutaneous electrical stimulation of the lumbosacral enlargement can improve trunk posture. Eight participants with non-progressive SCI at C3-T9, American Spinal Injury Association Impairment Scale (AIS) A or C, performed different motor tasks during sitting. Electromyography of the trunk muscles, three-dimensional kinematics, and force plate data were acquired. Spinal stimulation improved trunk control during sitting in all tested individuals. Stimulation resulted in elevated activity of the erector spinae, rectus abdominis, and external obliques, contributing to improved trunk control, more natural anterior pelvic tilt and lordotic curve, and greater multi-directional seated stability. During spinal stimulation, the center of pressure (COP) displacements decreased to 1.36 ± 0.98 mm compared with 4.74 ± 5.41 mm without stimulation (p = 0.0156) in quiet sitting, and the limits of stable displacement increased by 46.92 ± 35.66% (p = 0.0156), 36.92 ± 30.48% (p = 0.0156), 54.67 ± 77.99% (p = 0.0234), and 22.70 ± 26.09% (p = 0.0391) in the forward, backward, right, and left directions, respectively. During self-initiated perturbations, the correlation between anteroposterior arm velocity and the COP displacement decreased from r = 0.5821 (p = 0.0007) without to r = 0.5115 (p = 0.0039) with stimulation, indicating improved trunk stability. These data demonstrate that the spinal networks can be modulated transcutaneously with tonic electrical spinal stimulation to physiological states sufficient to generate a more stable, erect sitting posture after chronic paralysis.

Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis 1-3 . Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS) 4 . Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.

A hypothesis on the universal character of perceptual style for analyzing the surrounding space during sensory interactions has been tested. The indices of postural responses to moving and stationary auditory images in the groups of field-dependent and field-independent subjects, i.e., those who perceive spatial information about the object considering or ignoring the background, respectively, have been investigated. The differences in the sway parameters in both groups were revealed only in the case of moving auditory images. Body sway was more prominent in the group of field-independent subjects, whereas in the subjects from the field-dependent group, backward body displacement was observed during listening to approaching auditory images. Therefore, the perceptual style is reflected in the vertical postural responses to auditory information about the motion in the acoustic space.

We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task-specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side-lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Unlike prosthetic hearing, which develops technology for more than 30 years, the problem of the vestibular prosthesis developed a little more than one and half decades. Meanwhile, the involvement of the vestibular system in ensuring the normal functioning of the visual, motor and other systems of the body determines its decisive contribution to the spatial orientation of humans and animals. In case of damage of the vestibular apparatus (the labyrinth), there are serious violations of posture control, stabilization of sight, spatial orientation, psychological status, that is, in the aggregate quality of human life deteriorates. At present, on the animals developed technology of prosthetic semicircular canals, sensing angular acceleration, and control eye movements in dynamic situations. New approaches based on the replacement of the lost natural vestibular afferent impulses by electrical stimulation through multichannel vestibular prosthesis, are successfully introducing into the clinic.

Is it possible to regulate the functional properties of abnormally developed spinal neuronal locomotor networks using transcutaneous spinal cord stimulation? This question has been studied in twenty-eight participants (∼9 yrs) with spastic cerebral palsy, and mainly Gross Motor Function Classification System for Cerebral Palsy level III. The participants were randomly assigned to two groups. The experimental group received transcutaneous spinal cord stimulation at two spinal levels (over T11 and L1 spinous processes), combined with locomotor treadmill training, whereas the participants of the control group received locomotor treadmill training only. After spinal cord stimulation in the experimental group we found an incremental increase in knee torque whereas in the control group this effect was absent. The amplitude of hip motion increased in both groups. A decrease of co-activation of hip and muscles of the lower extremities was observed in the experimental group while in the control group co-activation decreased only in hip muscles. The results support the idea that locomotor function can be improved significantly with the combination of training and transcutaneous spinal cord stimulation than with training alone., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: The objective of the present study was to evaluate the influence of non-invasive (transcutaneous) electrical spinal cord stimulation on the locomotor function of the patients suffering from movement disorders., Patients and Methods: The study involved 10 patients of both sexes at the age from 32 to 70 years (including 40% of men and 60% of women) presenting with the compromised locomotor function of varying severity associated with the disturbances of cerebral blood circulation caused either by an injury to the brain and spinal cord or by stroke. The transcutaneous electrical spinal cord stimulation was applied using different frequency regimes with the placement of the electrodes in the projection onto the region of TXI-TXII vertebrae. The active factors were bipolar electrical stimuli 0.5 ms in duration; the current strength was chosen for each patient on an individual basis taking into consideration its threshold level. Electromyograms and evoked motor responses of selected muscles, viz. m. rectus femoris, m.biceps femoris, m. tibialis anterior, and m.gastrocnemius were recorded with the use of the 'Neuro-MVP-8 eight-channel electromyography' ('Neurosoft', Russia)., Results: The data obtained give evidence that the stimulation of the spinal cord with a frequency of 1 Hz induces reflectory responses with monosynaptic and polysynaptic components in the muscles of the lower extremities, with the thresholds of these responses being significantly higher in the patients presenting with serious neurological problems. Stimulation with the frequencies of 5 and 30 Hz caused in the patients with paresis the involuntary movement of the legs the characteristics of which were similar to those of the locomotor movements., Conclusion: It has been demonstrated that the application of transcutaneous electrical spinal cord stimulation leads to increased excitability of the lumbar spinal neural structures of the patients. The study has shown the possibility of regulation of the locomotor functions in the patients presenting with movement disorders of central genesis by means of non-invasive electrical stimulation of the spinal cord.

Recently transcutateous electrical spinal cord stimulation began to be used both for experimental studies of motor functions regulation and for rehabilitation of motor functions in patients with spinal cord injury. The spinal cord is a very important center of vital functions regulation and the spinal cord stimulation directed to the activation of spinal locomotor related networks will affect visceral systems as well. This circumstance is necessary to take into account when this new method will be used for rehabilitation as well as for the studies on healthy subjects. Here the review of publications related to effects of electrical spinal cord stimulation on peripheral and cerebral circulation, on the cardiovascular, respiratory, excretory, and digestive systems of mammals is presented.

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner., (Copyright © 2016. Published by Elsevier Inc.)

We analyzed the efficiency of percutaneous electrical stimulation of the spinal cord and serotonin receptor activation in rehabilitation of paralyzed patients. Four-week course of spinal cord electrical stimulation combined with mechanotherapy produced positive shifts in the status of chronically paralyzed patients. Serotonin receptor activation potentiated the effect of spinal cord stimulation and can be regarded as an additional neurorehabilitation option.

Cerebral palsy (CP) considerably impairs the ability to maintain upright stance. In the present study the effects of locomotor training and functional electrical stimulation (FES) on postural control have been determined in children (n = 27) aged 6–12 years with severe CP. The severity level of the CP clinical manifestations was determined as 3 according to the Gross Motor Function Classification System (GMFCS) classification. All patients participated in 15 half-hour sessions of mechanic therapy using robot-assisted passive stepping. In 12 out of 27 children, the locomotion therapy was accompanied with FES. Stabilometry and plantography tests were performed before and after the course of interventions. In addition, similar posturographics tests were performed in 23 healthy children same age. Postural control in children with CP was characterized by a forward shift of the center of pressure (COP) projection; higher values of the COP trajectory area and length, as weel as by mean amplitude of the COP oscillations, and the absence of COP response to the eyes closed condition. After treatment, the posturographic characteristics had a tendency to normalization in relation to the values obtained in neurologically intact children. The improvement was observed in 43% of children without FES and in 75% of children which used FES. Analysis of plantograms revealed normalization of footprints in children received FES. Thus, it was demonstrated that FES combined with locomotor training resulted in the improvement in vertical posture control in children with severe CP.

Multisegmental muscle responses (MMR) are reflexes in the leg muscles evoked by transcutaneous electrical spinal cord stimulation over the Th11–Th12 vertebrae. We have used MMR to evaluate the excitability of lumbosacral motor neurons in individuals suffering lower paraplegia. Ten individuals were tested using H-reflexes and MMR bilaterally before (n 0 = 20) and during 4-weeks course of rehabilitation (n=76). The H-reflex and MMR of m. gastrocnemius lateralis were obtained in: 15 and 13 cases out of 20, respectively. Both reflexes were recorded in 11 and were absent in 3 cases, matched up to 70% of recordings. In dynamic, the both methods were 100% reproducible and the responses’ amplitude varied in similar directions in 67% of records. The data confirm the validity and reproducibility of the MMR for evaluation of the motor neurons excitability in lumbosacral cord. The H-reflex magnitude shows moderate correlation with MMR in m. gastrocnemius lateralis (r = 0.59, p < 0.001), and low correlation with MMR in mm. rectus femoris, biceps femoris, and tibialis anterior (r < 0.40, p < 0.001). These findings do not allow extrapolate the results from the H-reflex measurement on the state of lumbosacral cord. At the same time, measurements of the MMR allow estimate simultaneously the excitability of motor pools innervating several muscle groups. This makes advantageous to assess the functional state of the motor neurons in the lumbosacral spinal cord for clinical and experimental studies, including the spinal cord damage.

We studied the interrelations between the activation of the receptors of musculoskeletal system and the spinal cord stimulation in the regulation of locomotor behavior in healthy subjects. We observed the effect of afferent stimulation on the patterns of stepping movements caused by percutaneous stimulation of spinal cord. It was found that the combination of percutaneous spinal cord stimulation and vibrostimulation increases the amplitude of leg movements. It was shown that the vibrostimulation of limb muscles at a frequency of less than 30 Hz may be used for comtrolling involuntary movements, caused by non-invasive stimulation of the spinal cord.

One of the cerebral palsy (CP) symptoms is the impairment of the ability to maintain upright standing. The objective of the present study was to investigate the effect of the locomotor training combined with electrical transcutaneous spinal cord stimulation (TSCS) and functional electrical stimulation (FES) of the muscles to facilitate the restoration of the vertical posture function in the children presenting with cerebral palsy., Patients and Methods: This article is designed to present the results of the study that included 19 patients at the age from 6 to 12 years. The severity of the CP clinical manifestations was estimated to be around 3 in accordance with The Gross Motor Function Classification System (GMFCS). All the patients underwent 15 half-hour daily sessions of robotic mechanotherapy with the use of a locomotor training device. In 8 patients from the main group, each locomotor training session was accompanied by the TSCS and FES procedures. The patients of the control group underwent the locomotor training alone., Results: The dynamics of regaining the standing posture regulation was evaluated by stabilometry that has revealed a significant increase of postural stability in the children of the main group in comparison with those in the control group. It was apparent as a statistically significant (p<0.05) reduction of the length and the area of the center of pressure (COP) projection with open eyes (the 167 mm and 112 mm2 decrease of the median, respectively). In addition, the tendency toward the normalization of the COP projection in the sagittal plane was documented., Conclusion: The present study has demonstrated the normalization of the impaired balance control system in the children presenting with the severe form of cerebral palsy under the influence of the combined treatment with the use of transcutaneous spinal cord stimulation and functional electrical stimulation of legs muscles supplemented by the locomotor training.

The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord.

It was demonstrated previously that transcutaneous electrical stimulation of multiple sites over the spinal cord is more effective in inducing robust locomotor behavior as compared to the stimulation of single sites alone in both animal and human models. To explore the effects and mechanisms of interactions during multi-site spinal cord stimulation we delivered transcutaneous electrical stimulation to the single or dual locations over the spinal cord corresponding to approximately L2 and S1 segments. Spinally evoked motor potentials in the leg muscles were investigated using single and paired pulses of 1ms duration with conditioning-test intervals (CTIs) of 5 and 50ms. We observed considerable post-stimulation modulatory effects which depended on CTIs, as well as on whether the paired stimuli were delivered at a single or dual locations, the rostro-caudal relation between the conditioning and test stimuli, and on the muscle studied. At CTI-5, the paired stimulation delivered at single locations (L2 or S1) provided strong inhibitory effects, evidenced by the attenuation of the compound responses as compared with responses from either single site. In contrast, during L2-S1 paradigm, the compound responses were potentiated. At CTI-50, the magnitude of inhibition did not differ among paired stimulation paradigms. Our results suggest that electrical stimuli delivered to dual sites over the lumbosacral enlargement in rostral-to-caudal order, may recruit different populations of motor neurons initially through projecting sensory and intraspinal connections and then directly, resulting in potentiation of the compound spinally evoked motor potentials. The interactive and synergistic effects indicate multi-segmental convergence of descending and ascending influences on the neuronal circuitries during electrical spinal cord stimulation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We asked whether coordinated voluntary movement of the lower limbs could be regained in an individual having been completely paralyzed (>4 yr) and completely absent of vision (>15 yr) using a novel strategy - transcutaneous spinal cord stimulation at selected sites over the spinal vertebrae with just one week of training. We also asked whether this stimulation strategy could facilitate stepping assisted by an exoskeleton (EKSO, EKSO Bionics) that is designed so that the subject can voluntarily complement the work being performed by the exoskeleton. We found that spinal cord stimulation enhanced the level of effort that the subject could generate while stepping in the exoskeleton. In addition, stimulation improved the coordination patterns of the lower limb muscles resulting in a more continuous, smooth stepping motion in the exoskeleton. These stepping sessions in the presence of stimulation were accompanied by greater cardiac responses and sweating than could be attained without the stimulation. Based on the data from this case study it appears that there is considerable potential for positive synergistic effects after complete paralysis by combining the overground stepping in an exoskeleton, a novel transcutaneous spinal cord stimulation paradigm, and daily training.

Cerebral palsy is one of the common diseases that cause significant motor impairments. This review deals with new methods of motor rehabilitation of children with cerebral palsy in terms of modern physiology, as well as with summarized and analyzed results of experimental studies on the effectiveness of these methods.

Transcutaneous and epidural electrical spinal cord stimulation techniques are becoming more valuable as electrophysiological and clinical tools. Recently, we observed selective activation of proximal and distal motor pools during epidural spinal stimulation. In the present study, we hypothesized that the characteristics of recruitment curves obtained from leg muscles will reflect a relative preferential activation of proximal and distal motor pools based on their arrangement along the lumbosacral enlargement. The purpose was to describe the electrophysiological responses to transcutaneous stimulation in leg muscles innervated by motoneurons from different segmental levels. Stimulation delivered along the rostrocaudal axis of the lumbosacral enlargement in the supine position resulted in a selective topographical recruitment of proximal and distal leg muscles, as described by threshold intensity, slope of the recruitment curves, and plateau point intensity and magnitude. Relatively selective recruitment of proximal and distal motor pools can be titrated by optimizing the site and intensity level of stimulation to excite a given combination of motor pools. The slope of the recruitment of particular muscles allows characterization of the properties of afferents projecting to specific motoneuron pools, as well as to the type and size of the motoneurons. The location and intensity of transcutaneous spinal electrical stimulation are critical to target particular neural structures across different motor pools in investigation of specific neuromodulatory effects. Finally, the asymmetry in bilateral evoked potentials is inevitable and can be attributed to both anatomical and functional peculiarities of individual muscles or muscle groups., (Copyright © 2015 the American Physiological Society.)

The musculoskeletal model of cat's hind limbs, capable to step while maintaining balance, was developed using the MatLab. The skeletal part of the model (spine, pelvis, hips, shanks, foots) was created at SimMechanics. The joint in the spine attachment to the support and hip joint have three degrees of freedom. Knee and ankle joints have one degree of freedom. The pelvis is rigidly connected to the spine. The control of the skeleton's segments is done by six groups of muscles (flexors and extensors of hips, knees and ankles), modeled using the package VirtualMuscle. The generalized lateral force exerted on the spine was introduced to compensate insecure lateral deviations. Experimental verification of the model realness have shown that its locomotor characteristics (e. g., muscles activation patterns, oscillation period of pelvis, correlation between step length and maximal lateral shift of pelvis) do not significantly differ from the locomotion of decerebrate cats. The simulation confirms the key role of lateral force evolved by paravertebral and abductor-adductor muscles in the control of lateral stability during locomotion.

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

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.

In quadrupeds, the most critical aspect of postural control during locomotion is lateral stability. However, neural mechanisms underlying lateral stability are poorly understood. Here, we studied lateral stability in decerebrate cats walking on a treadmill with their hindlimbs. Two destabilizing factors were used: a brief lateral push of the cat and a sustained lateral tilt of the treadmill. It was found that the push caused considerable trunk bending and twisting, as well as changes in the stepping pattern, but did not lead to falling. Due to postural reactions, locomotion with normal body configuration was restored in a few steps. It was also found that the decerebrate cat could keep balance during locomotion on the laterally tilted treadmill. This postural adaptation was based on the transformation of the symmetrical locomotor pattern into an asymmetrical one, with different functional lengths of the right and left limbs. Then, we analyzed limb and trunk neural mechanisms contributing to postural control during locomotion. It was found that one of the limb mechanisms operates in the transfer phase and secures a standard (relative to the trunk) position for limb landing. Two other limb mechanisms operate in the stance phase; they counteract distortions of the locomotor pattern by regulating the limb stiffness. The trunk configuration mechanism controls the body shape on the basis of sensory information coming from trunk afferents. We suggest that postural reactions generated by these four mechanisms are integrated, thus forming a response of the whole system to perturbation of balance during locomotion.

Epidural stimulation (ES) of the lumbosacral spinal cord has been used to facilitate standing and voluntary movement after clinically motor-complete spinal-cord injury. It seems of importance to examine how the epidurally evoked potentials are modulated in the spinal circuitry and projected to various motor pools. We hypothesized that chronically implanted electrode arrays over the lumbosacral spinal cord can be used to assess functionally spinal circuitry linked to specific motor pools. The purpose of this study was to investigate the functional and topographic organization of compound evoked potentials induced by the stimulation. Three individuals with complete motor paralysis of the lower limbs participated in the study. The evoked potentials to epidural spinal stimulation were investigated after surgery in a supine position and in one participant, during both supine and standing, with body weight load of 60%. The stimulation was delivered with intensity from 0.5 to 10 V at a frequency of 2 Hz. Recruitment curves of evoked potentials in knee and ankle muscles were collected at three localized and two wide-field stimulation configurations. Epidural electrical stimulation of rostral and caudal areas of lumbar spinal cord resulted in a selective topographical recruitment of proximal and distal leg muscles, as revealed by both magnitude and thresholds of the evoked potentials. ES activated both afferent and efferent pathways. The components of neural pathways that can mediate motor-evoked potentials were highly dependent on the stimulation parameters and sensory conditions, suggesting a weight-bearing-induced reorganization of the spinal circuitries.

Most bipeds and quadrupeds, in addition to forward walking, are also capable of backward and sideward walking. The direction of walking is determined by the direction of stepping movements of individual limbs in relation to the front-to-rear body axis. Our goal was to assess the functional organization of the system controlling the direction of stepping. Experiments were performed on decerebrate cats walking on the treadmill with their hindlimbs, whereas the head and trunk were rigidly fixed. Different directions of the treadmill motion relative to the body axis were used (0, ± 45, ± 90, and 180°). For each direction, we compared locomotion evoked from the brainstem (by stimulation of the mesencephalic locomotor region, MLR) with locomotion evoked by epidural stimulation of the spinal cord (SC). It was found that SC stimulation evoked well coordinated stepping movements at different treadmill directions. The direction of steps was opposite to the treadmill motion, suggesting that this direction was determined by sensory input from the limb during stance. Thus, SC stimulation activates limb controllers, which are able to generate stepping movements in different directions. By contrast, MLR stimulation evoked well coordinated stepping movements only if the treadmill was moving in the front-to-rear direction. One can conclude that supraspinal commands (caused by MLR stimulation) select one of the numerous forms of operation of the spinal limb controllers, namely, the forward walking. The MLR can thus be considered as a command center for forward locomotion, which is the main form of progression in bipeds and quadrupeds.

Until now, no scientific neurophysiologic methods of diagnostics and treatment of vertebrospinal pathologies were developed. Previous study showed that electrical stimulation of lumbar segments of the spinal cord in animals with complete spinal cord transection induced a well-coordinated weight-bearing locomotion. The present comparative study of motor activity triggered by electrical epidural stimulation of one or two segments of the spinal cord in spinal patients showed that stimulation of lumbar (L2-L4) or sacral (S2) segments facilitated generation of motor patterns of muscle activity. Combination of electrical stimulation with locomotor training resulted in the appearance of stepping patterns characteristic of normal walking and tonic activity of the muscles needed for body balance maintenance.

Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11-Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals.