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.

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.

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.

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.

Selectivity and excitability of upper-limb muscle activation during cervical transcutaneous spinal cord stimulation in humans.

Cervical transcutaneous spinal cord stimulation (tSCS) efficacy for rehabilitation of upper-limb motor function was suggested to depend on recruitment of Ia afferents. However, selectivity and excitability of motor activation with different electrode configurations remain unclear. In this study, activation of upper-limb motor pools was examined with different cathode and anode configurations during cervical tSCS in 10 able-bodied individuals. Muscle responses were measured from six upper-limb muscles simultaneously. First, postactivation depression was confirmed with tSCS paired pulses (50-ms interval) for each cathode configuration (C6, C7, and T1 vertebral levels), with anode on the anterior neck. Selectivity and excitability of activation of the upper-limb motor pools were examined by comparing the recruitment curves (10-100 mA) of first evoked responses across muscles and cathode configurations. Our results showed that hand muscles were preferentially activated when the cathode was placed over T1 compared with the other vertebral levels, whereas there was no selectivity for proximal arm muscles. Furthermore, higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles, suggesting different excitability thresholds between muscles. In a separate protocol, responses were compared between anode configurations (anterior neck, shoulders, iliac crests, and back), with one selected cathode configuration. The level of discomfort was also assessed. Largest muscle responses were elicited with the anode configuration over the anterior neck, whereas there were no differences in the discomfort. Our results therefore inform methodological considerations for electrode configuration to help optimize recruitment of Ia afferents during cervical tSCS.NEW & NOTEWORTHY We examined selectivity and excitability of motor activation in multiple upper-limb muscles during cervical transcutaneous spinal cord stimulation with different cathode and anode configurations. Hand muscles were more activated when the cathode was configured over the T1 vertebra compared with C6 and C7 locations. Higher stimulation intensities were required to activate distal hand muscles than proximal arm muscles. Finally, configuration of anode over anterior neck elicited larger responses compared with other configurations.

Transcutaneous spinal cord stimulation improves postural stability in individuals with multiple sclerosis.

BACKGROUND: Widespread demyelination in the central nervous system can lead to progressive sensorimotor impairments following multiple sclerosis, with compromised postural stability during standing being a common consequence. As such, clinical strategies are needed to improve postural stability following multiple sclerosis. The objective of this study was therefore to investigate the effect of non-invasive transcutaneous spinal stimulation on postural stability during upright standing in individuals with multiple sclerosis. METHODS: Center of pressure displacement and electromyograms from the soleus and tibialis anterior were recorded in seven individuals with multiple sclerosis during standing without and with transcutaneous spinal stimulation. Center of pressure and muscle activity measures were calculated and compared between no stimulation and transcutaneous spinal stimulation conditions. The relationship between the center of pressure displacement and electromyograms was quantified using cross-correlation analysis. RESULTS: For transcutaneous spinal stimulation, postural stability was significantly improved during standing with eyes closed: the time- and frequency-domain measures obtained from the anterior-posterior center of pressure fluctuation decreased and increased, respectively, and the tibialis anterior activity was lower compared to no stimulation. Conversely, no differences were found between no stimulation and transcutaneous spinal stimulation when standing with eyes open. CONCLUSION: Following multiple sclerosis, transcutaneous spinal stimulation improved postural stability during standing with eyes closed, presumably by catalyzing proprioceptive function. Future work should confirm underlying mechanisms and explore the clinical value of transcutaneous spinal stimulation for individuals with multiple sclerosis.

Quantitative Assessment of Clinician Assistance During Dynamic Rehabilitation Using Force Sensitive Resistors.

Background: Neuromodulation using epidural electrical stimulation (EES) has shown functional restoration in humans with chronic spinal cord injury (SCI). EES during body weight supported treadmill training (BWSTT) enhanced stepping performance in clinical trial participants with paraplegia. Unfortunately, tools are lacking in availability to quantify clinician assistance during BWSTT with and without EES. Force sensitive resistors (FSRs) have previously quantified clinician assistance during static standing; however, dynamic tasks have not been addressed. Objective: To determine the validity of FSRs in measurements of force and duration to quantify clinician assistance and participant progression during BWSTT with EES in participants with SCI. Design: A feasibility study to determine the effectiveness of EES to restore function in individuals with SCI. Methods: Two male participants with chronic SCI were enrolled in a pilot phase clinical trial. Following implantation of an EES system in the lumbosacral spinal cord, both participants underwent 12 months of BWSTT with EES. At monthly intervals, FSRs were positioned on participants' knees to quantity forces applied by clinicians to achieve appropriate mechanics of stepping during BWSTT. The FSRs were validated on the benchtop using a leg model instrumented with a multiaxial load cell as the gold standard. The outcomes included clinician-applied force duration measured by FSR sensors and changes in applied forces indicating progression over the course of rehabilitation. Results: The force sensitive resistors validation revealed a proportional bias in their output. Loading required for maximal assist training exceeded the active range of the FSRs but were capable of capturing changes in clinician assist levels. The FSRs were also temporally responsive which increased utility for accurately assessing training contact time. The FSRs readings were able to capture independent stance for both participants by study end. There was minimal to no applied force bilaterally for participant 1 and unilaterally for participant 2. Conclusions: Clinician assistance applied at the knees as measured through FSRs during dynamic rehabilitation and EES (both on and off) effectively detected point of contact and duration of forces; however, it lacks accuracy of magnitude assessment. The reduced contact time measured through FSRs related to increased stance duration, which objectively identified independence in stepping during EES-enabled BWSTT following SCI.

The relationship between maximum tolerance and motor activation during transcutaneous spinal stimulation is unaffected by the carrier frequency or vibration.

Transcutaneous spinal stimulation (TSS) is a useful tool to modulate spinal sensorimotor circuits and has emerged as a potential treatment for motor disorders in neurologically impaired populations. One major limitation of TSS is the discomfort associated with high levels of stimulation during the experimental procedure. The objective of this study was to examine if the discomfort caused by TSS can be alleviated using different stimulation paradigms in a neurologically intact population. Tolerance to TSS delivered using conventional biphasic balanced rectangular pulses was compared to two alternative stimulation paradigms: a 5 kHz carrier frequency and biphasic balanced rectangular pulses combined with vibrotactile stimulation. In ten healthy participants, tolerance to TSS was examined using both single-pulse (0.2 Hz) and continuous (30 Hz) stimulation protocols. In both the single-pulse and continuous stimulation protocols, participants tolerated significantly higher levels of stimulation with the carrier frequency paradigm compared to the other stimulation paradigms. However, when the maximum tolerable stimulation intensity of each stimulation paradigm was normalized to the intensity required to evoke a lower limb muscle response, there were no statistical differences between the stimulation paradigms. Our results suggest that, when considering the intensity of stimulation required to obtain spinally evoked motor potentials, neither alternative stimulation paradigm is more effective at reducing discomfort than the conventional, unmodulated pulse configuration.

Alterations of Spinal Epidural Stimulation-Enabled Stepping by Descending Intentional Motor Commands and Proprioceptive Inputs in Humans With Spinal Cord Injury.

Background: Regaining control of movement following a spinal cord injury (SCI) requires utilization and/or functional reorganization of residual descending, and likely ascending, supraspinal sensorimotor pathways, which may be facilitated via task-specific training through body weight supported treadmill (BWST) training. Recently, epidural electrical stimulation (ES) combined with task-specific training demonstrated independence of standing and stepping functions in individuals with clinically complete SCI. The restoration of these functions may be dependent upon variables such as manipulation of proprioceptive input, ES parameter adjustments, and participant intent during step training. However, the impact of each variable on the degree of independence achieved during BWST stepping remains unknown. Objective: To describe the effects of descending intentional commands and proprioceptive inputs, specifically body weight support (BWS), on lower extremity motor activity and vertical ground reaction forces (vGRF) during ES-enabled BWST stepping in humans with chronic sensorimotor complete SCI. Furthermore, we describe perceived changes in the level of assistance provided by clinicians when intent and BWS are modified. Methods: Two individuals with chronic, mid thoracic, clinically complete SCI, enrolled in an IRB and FDA (IDE G150167) approved clinical trial. A 16-contact electrode array was implanted in the epidural space between the T11-L1 vertebral regions. Lower extremity motor output and vertical ground reaction forces were obtained during clinician-assisted ES-enabled treadmill stepping with BWS. Consecutive steps were achieved during various experimentally-controlled conditions, including intentional participation and varied BWS (60% and 20%) while ES parameters remain unchanged. Results: During ES-enabled BWST stepping, the knee extensors exhibited an increase in motor activation during trials in which stepping was passive compared to active or during trials in which 60% BWS was provided compared to 20% BWS. As a result of this increased motor activation, perceived clinician assistance increased during the transition from stance to swing. Intentional participation and 20% BWS resulted in timely and purposeful activation of the lower extremities muscles, which improved independence and decreased clinician assistance. Conclusion: Maximizing participant intention and optimizing proprioceptive inputs through BWS during ES-enabled BWST stepping may facilitate greater independence during BWST stepping for individuals with clinically complete SCI. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02592668.

Preferential activation of spinal sensorimotor networks via lateralized transcutaneous spinal stimulation in neurologically intact humans.

Transcutaneous spinal stimulation (TSS), a noninvasive technique to modulate sensorimotor circuitry within the spinal cord, has been shown to enable a wide range of functions that were thought to be permanently impaired in humans with spinal cord injury. However, the extent to which TSS can be used to target specific mediolateral spinal cord circuitry remains undefined. We tested the hypothesis that TSS applied unilaterally to the skin ~2 cm lateral to the midline of the lumbosacral spine selectively activates ipsilateral spinal sensorimotor circuitry, resulting in ipsilateral activation of downstream lower extremity neuromusculature. TSS cathodes and anodes were positioned lateral from the midline of the spine in 15 healthy subjects while supine, and the timing of TSS pulses was synchronized to recordings of lower extremity muscle activity and force. At motor threshold, left and right TSS-evoked muscle activity was significantly higher in the ipsilateral leg compared with contralateral recordings from the same muscles. Similarly, we observed a significant increase in force production in the ipsilateral leg compared with the contralateral leg. Delivery of paired TSS pulses, during which an initial stimulus was applied to one side of the spinal cord and 50 ms later a second stimulus was applied to the contralateral side, revealed that ipsilateral leg muscle responses decreased following the initial stimulus, whereas contralateral muscle responses did not decrease, indicating side-specific activation of lateral spinal sensorimotor circuitry. Our results indicate TSS can selectively engage ipsilateral neuromusculature via lumbosacral sensorimotor networks responsible for lower extremity function in healthy humans.NEW & NOTEWORTHY We demonstrate the selectivity of transcutaneous spinal stimulation (TSS), which has been shown to enable function in humans with chronic paralysis. Specifically, we demonstrate that TSS applied to locations lateral to the spinal cord can selectively activate ipsilateral spinal sensorimotor networks. We quantified lumbosacral spinal network activity by recording lower extremity muscle electromyography and force. Our results suggest lumbosacral TSS engages side-specific spinal sensorimotor networks associated with ipsilateral lower extremity function in humans.