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.

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.

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.

Muscle Activation Patterns During Movement Attempts in Children With Acquired Spinal Cord Injury: Neurophysiological Assessment of Residual Motor Function Below the Level of Lesion.

Introduction: Characterization of residual neuromotor capacity after spinal cord injury (SCI) is challenging. The current gold standard for measurement of sensorimotor function after SCI, the International Society for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam, seeks to determine isolated intentional muscle activation, however many individuals with SCI exhibit intentional movements and muscle activation patterns which are not confined to specific joint or muscle. Further, isolated muscle activation is a feature of the neuromuscular system that emerges during development, and thus may not be an appropriate measurement standard for children younger than 6. Methods: We utilized neurophysiological assessment methodology, long studied in adult SCI populations, to evaluate residual neuromotor capacity in 24 children with SCI, as well as 19 typically developing (TD) children. Surface electromyography (EMG) signals were recorded from 11 muscles bilaterally, representing spinal motor output from all regions (i.e., cervical, thoracic, and lumbosacral), during standardized movement attempts. EMG records were subjectively analyzed based on spatiotemporal muscle activation characteristics, while the voluntary response index (VRI) was utilized for objective analysis of unilateral leg movement tasks. Results: Evidence of intentional leg muscle activation below the level of lesion was found in 11/24 children with SCI, and was classified based on activation pattern. Trace activation, bilateral (generalized) activation, and unilateral or isolated activation occurred in 32, 49, and 8% of movement tasks, respectively. Similarly, VRI analyses objectively identified significant differences between TD and SCI children in both magnitude (p < 0.01) and similarity index (p < 0.05) for all unilateral leg movement tasks. Activation of the erector spinae muscles, recorded at the T10-T12 vertebral level, was observed in all children with SCI, regardless of injury level or severity. Conclusions: Residual descending influence on spinal motor circuits may be present after SCI in children. Assessment of multi-muscle activation patterns during intentional movement attempts can provide objective evidence of the presence and extent of such residual muscle activation, and may provide an indicator of motor recovery potential following injury. The presence of residual intentional muscle activation has important implications for rehabilitation following pediatric-onset SCI.

Vestibulospinal and Corticospinal Modulation of Lumbosacral Network Excitability in Human Subjects.

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

Effects of paired transcutaneous electrical stimulation delivered at single and dual sites over lumbosacral spinal cord.

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

Spinal segment-specific transcutaneous stimulation differentially shapes activation pattern among motor pools in humans.

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

Hindlimb stretching alters locomotor function after spinal cord injury in the adult rat.

BACKGROUND: Stretching is a widely accepted standard-of-care therapy following spinal cord injury (SCI) that has not been systematically studied in animal models. OBJECTIVE: To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI. METHODS: A randomized treatment and control study of stretching in an animal model of acute SCI. Moderate SCIs were delivered with the NYU Impactor. Daily stretching (30 min/day, 5 days/wk for 8 weeks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer. RESULTS: Declines in hindlimb function during overground stepping were observed for the first 4 weeks for stretched animals. BBB scores improved weeks 5 to 10 but remained below the control group. Stretched animals had significant deficits in knee passive range of motion starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5. CONCLUSION: Stretch-based therapy significantly impaired functional recovery in adult rats with a moderate contusive SCI at T10. The negative impact on function was greatest acutely but persisted even after the stretching ceased at 8 weeks postinjury.