Ventral epidural stimulation for motor recovery after spinal cord injury: illustrative case.

BACKGROUND: Spinal cord stimulation (SCS) has demonstrated potential as a therapy to enhance motor functional recovery after spinal cord injury (SCI). Epidural SCS for motor recovery is traditionally performed via the dorsal electrode. While ventral epidural stimulation may provide more direct and specific stimulation of the ventral motor neurons involved in motor control, it is largely unstudied, and its role in motor recovery after SCI is unclear. In order to profile the safety and feasibility of ventral epidural spinal stimulation (VSS), the authors present a patient who underwent VSS following a corpectomy to treat SCI related to metastatic epidural cord compression. OBSERVATIONS: A patient underwent transpedicular corpectomy for spinal cord decompression, as well as the placement of 2 ventral epidural electrodes, followed by concurrent physical therapy and ventral epidural stimulation. He was nonambulatory preoperatively but was able to walk over 300 feet with the assistance of a rolling walker at the conclusion of the 3-week study period. VSS was noted to produce improvements in muscle contraction when stimulation was on. LESSONS: VSS appears to be safe, feasible, and well tolerated. VSS, as compared to standard-of-care therapy for SCI, can be used in conjunction with physical therapy and may lead to improvements in motor function. https://thejns.org/doi/10.3171/CASE24155.

Assessing the Effect of Cervical Transcutaneous Spinal Stimulation With an Upper Limb Robotic Exoskeleton and Surface Electromyography.

Transcutaneous spinal stimulation (TSS) is a promising rehabilitative intervention to restore motor function and coordination for individuals with spinal cord injury (SCI). The effects of TSS are most commonly assessed by evaluating muscle response to stimulation using surface electromyography (sEMG). Given the increasing use of robotic devices to deliver therapy and the emerging potential of hybrid rehabilitation interventions that combine neuromodulation with robotic devices, there is an opportunity to leverage the on-board sensors of the robots to measure kinematic and torque changes of joints in the presence of stimulation. This paper explores the potential for robotic assessment of the effects of TSS delivered to the cervical spinal cord. We used a four degree-of-freedom exoskeleton to measure the torque response of upper limb (UL) joints during stimulation, while simultaneously recording sEMG. We analyzed joint torque and electromyography data generated during TSS delivered over individual sites of the cervical spinal cord in neurologically intact participants. We show that site-specific effects of TSS are manifested not only by modulation of the amplitude of spinally evoked motor potentials in UL muscles, but also by changes in torque generated by individual UL joints. We observed preferential resultant action of proximal muscles and joints with stimulation at the rostral site, and of proximal joints with rostral-lateral stimulation. Robotic assessment can be used to measure the effects of TSS, and could be integrated into complex control algorithms that govern the behavior of hybrid neuromodulation-robotic systems.

A novel minimally invasive and versatile kyphoplasty balloon-based model of porcine spinal cord injury.

Introduction: Spinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios. Methods: We developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery. Results: The model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury. Discussion: Few large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype.

Synergistic effects of transcutaneous spinal stimulation and neuromuscular electrical stimulation on lower limb force production: Time to deliver.

BACKGROUND: Transcutaneous spinal stimulation (TSS) and neuromuscular electrical stimulation (NMES) can facilitate self-assisted standing in individuals with paralysis. However, individual variability in responses to each modality may limit their effectiveness in generating the necessary leg extension force for full body weight standing. To address this challenge, we proposed combining TSS and NMES to enhance leg extensor muscle activation, with optimizing timing adjustment to maximize the interaction between the two modalities. METHODS: To assess the effects of TSS and NMES on knee extension and plantarflexion force, ten neurologically intact participants underwent three conditions: (1) TSS control, (2) NMES control, and (3) TSS + NMES. TSS was delivered between the T10 and L2 vertebrae, while NMES was delivered to the skin over the right knee extensors and plantarflexors. TSS and NMES were administered using a 15 Hz train of three 0.5 ms biphasic pulses. During the TSS + NMES condition, the timing between modalities was adjusted in increments of » the interval within a 15 Hz frequency, i.e., 66, 49.5, 33, 16.5, and 1 ms. RESULTS: NMES combined with TSS, produced synergistic effects even on non-targeted muscle groups, thereby promoting leg extension across multiple joints in the kinematic chain. The sequence of NMES or TSS trains relative to each other did not significantly impact motor output. Notably, a delay of 16.5 to 49.5 ms between interleaved TSS and NMES pulses, each delivered at 15 Hz, results in more robust and synergistic responses in knee extensors and plantarflexors. CONCLUSIONS: By adjusting the timing between TSS and NMES, we can optimize the combined use of these modalities for functional restoration. Our findings highlight the potential of integrated TSS and NMES protocols to enhance motor function, suggesting promising avenues for therapeutic applications, particularly in the rehabilitation of individuals with SCI.

Synergistic implications of combinatorial rehabilitation approaches using spinal stimulation on therapeutic outcomes in spinal cord injury.

OBJECTIVE: The objective of this narrative review was to locate and assess recent articles employing a combinatorial approach of transcutaneous spinal cord stimulation or epidural spinal cord stimulation with additional modalities. We sought to provide relevant knowledge of recent literature and advance understanding on outcomes reported, to better equip those working in neurorehabilitation and neuromodulation. METHODS: Articles were selected and analyzed based on study approach, stimulation parameters, outcome measures, and presence of neurophysiological data to support findings. RESULTS: This narrative review analyzed 44 recent articles employing a combinatorial approach of transcutaneous spinal cord stimulation or epidural spinal cord stimulation with additional modalities. Our findings showed that limited research exists regarding such combinatorial approaches, particularly when considering modalities beyond activity-based training. There is also limited consistency in neurophysiological and quality of life outcomes. CONCLUSION: Articles involving transcutaneous spinal cord stimulation or epidural spinal cord stimulation with other modalities are limited in the current body of literature. Authors noted variety in approach, sample size, and use of participant perspective. Opportunities are present to add high quality research to this body of literature. SIGNIFICANCE: Transcutaneous spinal cord stimulation and epidural spinal cord stimulation are emerging in research as viable avenues for targeting improvement of function after traumatic spinal cord injury, particularly when combined with activity-based training. This body of literature demonstrates viable areas for growth from both neurophysiological and functional perspectives. Further, exploration of novel combinatorial approaches holds potential to offer enhanced contributions to clinical and neurophysiological rehabilitation and research.

Modulations in neural pathways excitability post transcutaneous spinal cord stimulation among individuals with spinal cord injury: a systematic review.

Introduction: Transcutaneous spinal cord stimulation (TSCS), a non-invasive form of spinal cord stimulation, has been shown to improve motor function in individuals living with spinal cord injury (SCI). However, the effects of different types of TSCS currents including direct current (DC-TSCS), alternating current (AC-TSCS), and spinal paired stimulation on the excitability of neural pathways have not been systematically investigated. The objective of this systematic review was to determine the effects of TSCS on the excitability of neural pathways in adults with non-progressive SCI at any level. Methods: The following databases were searched from their inception until June 2022: MEDLINE ALL, Embase, Web of Science, Cochrane Library, and clinical trials. A total of 4,431 abstracts were screened, and 23 articles were included. Results: Nineteen studies used TSCS at the thoracolumbar enlargement for lower limb rehabilitation (gait & balance) and four studies used cervical TSCS for upper limb rehabilitation. Sixteen studies measured spinal excitability by reporting different outcomes including Hoffmann reflex (H-reflex), flexion reflex excitability, spinal motor evoked potentials (SMEPs), cervicomedullay evoked potentials (CMEPs), and cutaneous-input-evoked muscle response. Seven studies measured corticospinal excitability using motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS), and one study measured somatosensory evoked potentials (SSEPs) following TSCS. Our findings indicated a decrease in the amplitude of H-reflex and long latency flexion reflex following AC-TSCS, alongside an increase in the amplitudes of SMEPs and CMEPs. Moreover, the application of the TSCS-TMS paired associative technique resulted in spinal reflex inhibition, manifested by reduced amplitudes in both the H-reflex and flexion reflex arc. In terms of corticospinal excitability, findings from 5 studies demonstrated an increase in the amplitude of MEPs linked to lower limb muscles following DC-TSCS, in addition to paired associative stimulation involving repetitive TMS on the brain and DC-TSCS on the spine. There was an observed improvement in the latency of SSEPs in a single study. Notably, the overall quality of evidence, assessed by the modified Downs and Black Quality assessment, was deemed poor. Discussion: This review unveils the systematic evidence supporting the potential of TSCS in reshaping both spinal and supraspinal neuronal circuitries post-SCI. Yet, it underscores the critical necessity for more rigorous, high-quality investigations.

Multi-site lumbar transcutaneous spinal cord stimulation: When less is more.

BACKGROUND: Transcutaneous spinal stimulation (TSS) has become a valuable tool for facilitating rehabilitation in individuals with neurological deficits. A significant constraint arises from the need for precise knowledge of stimulation locations to effectively apply TSS for targeted functional enhancement. METHODS: In this study, we investigate whether single-site or simultaneous multi-site stimulation over the lumbar spinal cord is advantageous for recruitment of specific motor pools projecting to lower limb muscles and generates higher leg extensor forces in neurologically intact individuals. Tests were performed in a supine position. TSS was delivered at T10-T11, T11-T12, T12-L1, and L1-L2 intervertebral spaces individually, then through all four locations simultaneously. The peak-to-peak amplitude of spinally evoked motor potentials and the forces generated by lower limb muscles were compared at the common motor threshold intensity level across all stimulation conditions. RESULTS: Recruitment of motor pools projecting to proximal and distal lower limb muscles followed their topographical rostro-caudal arrangement along the lumbosacral enlargement. Single-site stimulation, apart from the T10-T11 location, resulted in larger responses in both proximal and distal muscles while also generating higher knee-extension and plantarflexion forces when compared to multi-site stimulation. CONCLUSIONS: Both motor response and force generation were reduced when using multi-site TSS when compared to single-site stimulation. This demonstrates that the segmental effects of TSS are important to consider when performing multi-site TSS.

Characterizing neurological status in individuals with tetraplegia using transcutaneous spinal stimulation.

Transcutaneous spinal stimulation (TSS) is emerging as a valuable tool for electrophysiological and clinical assessment. This study had the objective of examining the recruitment patterns of upper limb (UL) motor pools through the delivery of TSS above and below a spinal lesion. It also aimed to explore the connection between the recruitment pattern of UL motor pools and the neurological and functional status following spinal cord injury (SCI). In eight participants with tetraplegia due to cervical SCI, TSS was delivered to the cervical spinal cord between the spinous processes of C3-C4 and C7-T1 vertebrae, and spinally evoked motor potentials in UL muscles were characterized. We found that responses observed in UL muscles innervated by motor pools below the level of injury demonstrated relatively reduced sensitivity to TSS compared to those above the lesion, were asymmetrical in the majority of muscles, and were dependent on the level, extent, and side of SCI. Overall, our findings indicate that electrophysiological data acquired through TSS can offer insights into the extent of UL functional asymmetry, disruptions in neural pathways, and changes in motor control following SCI. This study suggests that such electrophysiological data can supplement clinical and functional assessment and provide further insight regarding residual motor function in individuals with SCI.

Transcutaneous spinal stimulation provides characterization of neurological status in individuals with tetraplegia.

Transcutaneous spinal stimulation (TSS) is emerging as a valuable tool for electrophysiological and clinical assessment. This study had the objective of examining the recruitment patterns of upper limb (UL) motor pools through the delivery of TSS above and below a spinal lesion. It also aimed to explore the connection between the recruitment pattern of UL motor pools and the neurological and functional status following spinal cord injury (SCI). In eight participants with tetraplegia due to cervical SCI, TSS was delivered to the cervical spinal cord between the spinous processes of C3-C4 and C7-T1 vertebrae, and spinally evoked motor potentials in UL muscles were characterized. We found that responses observed in UL muscles innervated by motor pools below the level of injury demonstrated relatively reduced sensitivity to TSS compared to those above the lesion, were asymmetrical in the majority of muscles, and were dependent on the level, extent, and side of SCI. Overall, our findings indicate that electrophysiological data acquired through TSS can offer insights into the extent of UL functional asymmetry, disruptions in neural pathways, and changes in motor control following SCI. This study suggests that such electrophysiological data can supplement clinical and functional assessment and provide further insight regarding residual motor function in individuals with SCI.

Corrigendum: Impact of different ground-based microgravity models on human sensorimotor system.

[This corrects the article DOI: 10.3389/fphys.2023.1085545.].

Sensory organization of postural control after long term space flight.

Background: Alterations in motor control systems is an inevitable consequence of space flights of any duration. After the flight, the crew-members have significant difficulties with maintaining upright balance and locomotion, which last several days following landing. At the same time, the specific mechanisms of these effects remain unclear. Objectives: The aim of the study was to assess effects of long-term space flight on postural control and to define the changes of sensory organization caused by microgravity. Methods: 33 cosmonauts of Russian Space Agency, the members of International Space Station (ISS) flights of duration between 166 and 196 days took part in this study. Computerized Dynamic Posturography (CDP) tests, which include assessment of visual, proprioceptive and vestibular function in postural stability, was performed twice before the flight and on the 3rd, 7th, and 10th days after landing. The video analysis of ankle and hip joints fluctuations was performed to investigate the basis of postural changes. Results: Exposure to long-term space flight was followed by considerable changes of postural stability (-27% of Equilibrium Score value in the most complicated test, SOT5m). Changes in postural strategies to maintain balance were observed in the tests which provide the challenge for vestibular system. In particular, increased hip joint involvement (+100% in median value and +135% in 3rd quartile of hip angle fluctuation RMS in SOT5m) into postural control process was revealed. Conclusion: Decrease of postural stability after long-term space flight was associated with alterations in vestibular system and biomechanically was revealed by increased hip strategy which is less accurate, but simpler in terms of the central control.

Impact of different ground-based microgravity models on human sensorimotor system.

This review includes current and updated information about various ground-based microgravity models and their impact on the human sensorimotor system. All known models of microgravity are imperfect in a simulation of the physiological effects of microgravity but have their advantages and disadvantages. This review points out that understanding the role of gravity in motion control requires consideration of data from different environments and in various contexts. The compiled information can be helpful to researchers to effectively plan experiments using ground-based models of the effects of space flight, depending on the problem posed.

Combinatorial Effects of Transcutaneous Spinal Stimulation and Task-Specific Training to Enhance Hand Motor Output after Paralysis.

Background: Despite the positive results in upper limb (UL) motor recovery after using electrical neuromodulation in individuals after cervical spinal cord injury (SCI) or stroke, there has been limited exploration of potential benefits of combining task-specific hand grip training with transcutaneous electrical spinal stimulation (TSS) for individuals with UL paralysis. Objectives: This study investigates the combinatorial effects of task-specific hand grip training and noninvasive TSS to enhance hand motor output after paralysis. Methods: Four participants with cervical SCI classified as AIS A and B and two participants with cerebral stroke were recruited in this study. The effects of cervical TSS without grip training and during training with sham stimulation were contrasted with hand grip training with TSS. TSS was applied at midline over cervical spinal cord. During hand grip training, 5 to 10 seconds of voluntary contraction were repeated at a submaximum strength for approximately 10 minutes, three days per week for 4 weeks. Signals from hand grip dynamometer along with the electromyography (EMG) activity from UL muscles were recorded and displayed as visual feedback. Results: Our case study series demonstrated that combined task-specific hand grip training and cervical TSS targeting the motor pools of distal muscles in the UL resulted in significant improvements in maximum hand grip strength. However, TSS alone or hand grip training alone showed limited effectiveness in improving grip strength. Conclusion: Task-specific hand grip training combined with TSS can result in restoration of hand motor function in paralyzed upper limbs in individuals with cervical SCI and stroke.

Combining transcutaneous spinal stimulation and functional electrical stimulation increases force generated by lower limbs: When more is more.

Background: Transcutaneous Spinal Stimulation (TSS) has been shown to promote activation of the lower limb and trunk muscles and is being actively explored for improving the motor outcomes of people with neurological conditions. However, individual responses to TSS vary, and often the muscle responses are insufficient to produce enough force for self-supported standing. Functional electrical stimulation (FES) can activate individual muscles and assist in closing this functional gap, but it introduces questions regarding timing between modalities. Methods: To assess the effects of TSS and FES on force generation, ten neurologically intact participants underwent (1) TSS only, (2) FES only, and (3) TSS + FES. TSS was delivered using four electrodes placed at T10-T11 through the L1-L2 intervertebral spaces simultaneously, while FES was delivered to the skin over the right knee extensors and plantarflexors. For all conditions, TSS and FES were delivered using three 0.5 ms biphasic square-wave pulses at 15 Hz. During the TSS + FES condition, timing between the two modalities was adjusted in increments of » time between pulses (16.5 ms). Results: When TSS preceded FES, a larger force production was observed. We also determined several changes in muscle activation amplitude at different relative stimulus intervals, which help characterize our finding and indicate the facilitating and inhibitory effects of the modalities. Conclusions: Utilizing a delay ranging from 15 to 30 ms between stimuli resulted in higher mean force generation in both the knee and ankle joints, regardless of the selected FES location (Average; knee: 112.0%, ankle: 103.1%).

Transcutaneous spinal stimulation alters cortical and subcortical activation patterns during mimicked-standing: A proof-of-concept fMRI study.

Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation technique that has been used to facilitate the performance of voluntary motor functions such as trunk control and self-assisted standing in individuals with spinal cord injury. Although it is hypothesized that TSS amplifies signals from supraspinal motor control networks, the effect of TSS on supraspinal activation patterns is presently unknown. The purpose of this study was to investigate TSS-induced activity in supraspinal sensorimotor regions during a lower-limb motor task. Functional magnetic resonance imaging (fMRI) was used to assess changes in neural activation patterns as eleven participants performed mimicked-standing movements in the scanner. Movements were performed without stimulation, as well as in the presence of (1) TSS, (2) stimulation applied to the back muscle, (3) paresthesia stimulation, and (4) neuromuscular electrical stimulation. TSS was associated with greater activation in subcortical and cortical sensorimotor regions involved in relay and processing of movement-related somatosensory information (e.g., thalamus, caudate, pallidum, putamen), as compared to the other stimulation paradigms. TSS also resulted in deactivation in both nucleus accumbens and posterior parietal cortex, suggesting a shift toward somatosensory feedback-based mechanisms and more reflexive motor control. Together, these findings demonstrate that spinal stimulation can alter the activity within supraspinal sensorimotor networks and promote the use of somatosensory feedback, thus providing a plausible neural mechanism for the stimulation-induced improvements of sensorimotor function observed in participants with neurological injuries and disorders.

Measuring Torque Production with a Robotic Exoskeleton during Cervical Transcutaneous Spinal Stimulation.

Spinal cord injury (SCI) affects a large number of individuals in the United States. Unfortunately, traditional neurorehabilitation therapy leaves out clinical populations with limited motor function, such as severe stroke or spinal cord injury, as they are incapable of engaging in movement therapy. To increase the numbers of individuals who may be able to participate in robotic therapy, our long-term goal is to combine two validated interventions, transcutaneous spinal stimulation (TSS) and robotics, to elicit upper limb movements during rehabilitation following SCI. To achieve this goal, it is necessary to quantify the contributions of each intervention to realizing arm movements. Electromyography is typically used to assess the response to TSS, but the robot itself offers an additional source of data since the available sensors on the robot can be used to directly assess resultant actions of the upper limb after stimulation. We explore this approach in this paper. We showed that the effects of cutaneous TSS can be observed by measuring the holding torque required by the exoskeleton to keep a user's arm in a neutral position. Further, we can identify differences in resultant action based on the location of the stimulation electrodes with respect to the dorsal roots of the spinal cord. In the future, we can use measurements from the robot to guide the action of the robot and TSS intervention.

Cervical transcutaneous spinal stimulation for spinal motor mapping.

Transcutaneous spinal stimulation (TSS) is a promising approach to restore upper-limb (UL) functions after spinal cord injury (SCI) in humans. We sought to demonstrate the selectivity of recruitment of individual UL motor pools during cervical TSS using different electrode placements. We demonstrated that TSS delivered over the rostrocaudal and mediolateral axes of the cervical spine resulted in a preferential activation of proximal, distal, and ipsilateral UL muscles. This was revealed by changes in motor threshold intensity, maximum amplitude, and the amount of post-activation depression of the evoked responses. We propose that an arrangement of electrodes targeting specific UL motor pools may result in superior efficacy, restoring more diverse motor activities after neurological injuries and disorders, including severe SCI.

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study.

Objective.Transcutaneous spinal cord stimulation (TSS) has been shown to be a promising non-invasive alternative to epidural spinal cord stimulation for improving outcomes of people with spinal cord injury (SCI). However, studies on the effects of TSS on cortical activation are limited. Our objectives were to evaluate the spatiotemporal effects of TSS on brain activity, and determine changes in functional connectivity under several different stimulation conditions. As a control, we also assessed the effects of functional electrical stimulation (FES) on cortical activity.Approach. Non-invasive scalp electroencephalography (EEG) was recorded during TSS or FES while five neurologically intact participants performed one of three lower-limb tasks while in the supine position: (1) A no contraction control task, (2) a rhythmic contraction task, or (3) a tonic contraction task. After EEG denoising and segmentation, independent components (ICs) were clustered across subjects to characterize sensorimotor networks in the time and frequency domains. ICs of the event related potentials (ERPs) were calculated for each cluster and condition. Next, a Generalized Partial Directed Coherence (gPDC) analysis was performed on each cluster to compare the functional connectivity between conditions and tasks.Main results. IC analysis of EEG during TSS resulted in three clusters identified at Brodmann areas (BA) 9, BA 6, and BA 4, which are areas associated with working memory, planning, and movement control. Lastly, we found significant (p < 0.05, adjusted for multiple comparisons) increases and decreases in functional connectivity of clusters during TSS, but not during FES when compared to the no stimulation conditions.Significance.The findings from this study provide evidence of how TSS recruits cortical networks during tonic and rhythmic lower limb movements. These results have implications for the development of spinal cord-based computer interfaces, and the design of neural stimulation devices for the treatment of pain and sensorimotor deficit.

Minimal handgrip force is needed for transcutaneous electrical stimulation to improve hand functions of patients with severe spinal cord injury.

Spinal cord stimulation enhanced restoration of motor function following spinal cord injury (SCI) in unblinded studies. To determine whether training combined with transcutaneous electrical spinal cord stimulation (tSCS), with or without systemic serotonergic treatment with buspirone (busp), could improve hand function in individuals with severe hand paralysis following SCI, we assessed ten subjects in a double-blind, sham-controlled, crossover study. All treatments-busp, tSCS, and the busp plus tSCS-reduced muscle tone and spasm frequency. Buspirone did not have any discernible impact on grip force or manual dexterity when administered alone or in combination with tSCS. In contrast, grip force, sinusoidal force generation and grip-release rate improved significantly after 6 weeks of tSCS in 5 out of 10 subjects who had residual grip force within the range of 0.1-1.5 N at the baseline evaluation. Improved hand function was sustained in subjects with residual grip force 2-5 months after the tSCS and buspirone treatment. We conclude that tSCS combined with training improves hand strength and manual dexterity in subjects with SCI who have residual grip strength greater than 0.1 N. Buspirone did not significantly improve the hand function nor add to the effect of stimulation.