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.

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%).

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.

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.

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.

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.

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.

Characterization of interlimb interaction via transcutaneous spinal stimulation of cervical and lumbar spinal enlargements.

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.

Characterization of Spinal Sensorimotor Network Using Transcutaneous Spinal Stimulation during Voluntary Movement Preparation and Performance.

Transcutaneous electrical spinal stimulation (TSS) can be used to selectively activate motor pools based on their anatomical arrangements in the lumbosacral enlargement. These spatial patterns of spinal motor activation may have important clinical implications, especially when there is a need to target specific muscle groups. However, our understanding of the net effects and interplay between the motor pools projecting to agonist and antagonist muscles during the preparation and performance of voluntary movements is still limited. The present study was designed to systematically investigate and differentiate the multi-segmental convergence of supraspinal inputs on the lumbosacral neural network before and during the execution of voluntary leg movements in neurologically intact participants. During the experiments, participants (N = 13) performed isometric (1) knee flexion and (2) extension, as well as (3) plantarflexion and (4) dorsiflexion. TSS consisting of a pair pulse with 50 ms interstimulus interval was delivered over the T12-L1 vertebrae during the muscle contractions, as well as within 50 to 250 ms following the auditory or tactile stimuli, to characterize the temporal profiles of net spinal motor output during movement preparation. Facilitation of evoked motor potentials in the ipsilateral agonists and contralateral antagonists emerged as early as 50 ms following the cue and increased prior to movement onset. These results suggest that the descending drive modulates the activity of the inter-neuronal circuitry within spinal sensorimotor networks in specific, functionally relevant spatiotemporal patterns, which has a direct implication for the characterization of the state of those networks in individuals with neurological conditions.

Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with 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.

Low-Intensity and Short-Duration Continuous Cervical Transcutaneous Spinal Cord Stimulation Intervention Does Not Prime the Corticospinal and Spinal Reflex Pathways in Able-Bodied Subjects.

Cervical transcutaneous spinal cord stimulation (tSCS) has been utilized in applications for improving upper-limb sensory and motor function in patients with spinal cord injury. Although therapeutic effects of continuous cervical tSCS interventions have been reported, neurophysiological mechanisms remain largely unexplored. Specifically, it is not clear whether sub-threshold intensity and 10-min duration continuous cervical tSCS intervention can affect the central nervous system excitability. Therefore, the purpose of this study was to investigate effects of sub-motor-threshold 10-min continuous cervical tSCS applied at rest on the corticospinal and spinal reflex circuit in ten able-bodied individuals. Neurophysiological assessments were conducted to investigate (1) corticospinal excitability via transcranial magnetic stimulation applied on the primary motor cortex to evoke motor-evoked potentials (MEPs) and (2) spinal reflex excitability via single-pulse tSCS applied at the cervical level to evoke posterior root muscle (PRM) reflexes. Measurements were recorded from multiple upper-limb muscles before, during, and after the intervention. Our results showed that low-intensity and short-duration continuous cervical tSCS intervention applied at rest did not significantly affect corticospinal and spinal reflex excitability. The stimulation duration and/or intensity, as well as other stimulating parameters selection, may therefore be critical for inducing neuromodulatory effects during cervical tSCS.