Trans-spinal Stimulation Research Articles

Non-invasive central nervous system stimulation to improve bladder and pelvic floor function in the aging population.

The literature was reviewed for all noninvasive central nervous system (CNS) stimulation techniques, which includes transcranial brain or trans-spinal stimulation, in the aging population. Given the rising ubiquity of this technology, noninvasive nature, and low side-effect profile reported, this technology can have a big impact on the aging population. As patients afflicted with neurogenic disorders are living longer lives, a special emphasis is placed on the aging neurogenic population. Noninvasive CNS stimulation techniques have been applied to major bladder and pelvic floor disorders such as voiding dysfunction, chronic pelvic pain, urgency and urge incontinence, lower urinary tract dysfunction, and situational urge incontinence in both the idiopathic and neurogenic populations. Overall, these noninvasive technologies demonstrate effectiveness for the treatment of these conditions with some studies showing effectiveness with longer-term follow-up suggesting lasting CNS remodeling. Most manuscripts had a generally small number of patients and an even smaller number of geriatric patients represented. No studies were specifically designed to investigate geriatric outcomes. It is the hope of this systematic review to help model future studies according to existing literature, but with a focus on the geriatric population as they stand to gain the most from noninvasive technologies with limited adverse events.

Interactions between arm and leg neuronal circuits following paired cervical and lumbosacral transspinal stimulation in healthy humans.

Transspinal (or transcutaneous spinal cord) stimulation is a promising noninvasive method that may strengthen the intrinsic spinal neural connectivity in neurological disorders. In this study we assessed the effects of cervical transspinal stimulation on the amplitude of leg transspinal evoked potentials (TEPs), and the effects of lumbosacral transspinal stimulation on the amplitude of arm TEPs. Control TEPs were recorded following transspinal stimulation with one cathode electrode placed either on Cervical 3 (21.3 ± 1.7mA) or Thoracic 10 (23.6 ± 16.5mA) vertebrae levels. Associated anodes were placed bilaterally on clavicles or iliac crests. Cervical transspinal conditioning stimulation produced short latency inhibition of TEPs recorded from left soleus (ranging from - 6.11 to -3.87% of control TEP at C-T intervals of -50, -25, -20, -15, -10, 15 ms), right semitendinosus (ranging from - 11.1 to -4.55% of control TEP at C-T intervals of -20, -15, 15 ms), and right vastus lateralis (ranging from - 13.3 to -8.44% of control TEP at C-T intervals of -20 and - 15 ms) (p < 0.05). Lumbosacral transspinal conditioning stimulation produced no significant effects on arm TEPs. We conclude that in the resting state, cervical transspinal stimulation affects the net motor output of leg motoneurons under the experimental conditions used in this study. Further investigations are warranted to determine whether this protocol may reactivate local spinal circuitry after stroke or spinal cord injury and may have a significant effect in synchronization of upper and lower limb muscle synergies during rhythmic activities like locomotion or cycling.

Postsynaptic potentials of soleus motor neurons produced by transspinal stimulation: a human single-motor unit study.

Transspinal (or transcutaneous spinal cord) stimulation is a noninvasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and nonsomatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single-pulse transspinal stimulation using single-motor unit (SMU) discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram, and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions.NEW & NOTEWORTHY Transspinal stimulation produces distinct actions on soleus motor neurons: an early short-latency excitation followed by two inhibitions or only inhibition and doublets. These results show how transspinal stimulation affects depolarization of soleus α motor neurons in healthy humans.

Tapping into the human spinal locomotor centres with transspinal stimulation

Human locomotion is controlled by spinal neuronal networks of similar properties, function, and organization to those described in animals. Transspinal stimulation affects the spinal locomotor networks and is used to improve standing and walking ability in paralyzed people. However, the function of locomotor centers during transspinal stimulation at different frequencies and intensities is not known. Here, we document the 3D joint kinematics and spatiotemporal gait characteristics during transspinal stimulation at 15, 30, and 50 Hz at sub-threshold and supra-threshold stimulation intensities. We document the temporal structure of gait patterns, dynamic stability of joint movements over stride-to-stride fluctuations, and limb coordination during walking at a self-selected speed in healthy subjects. We found that transspinal stimulation (1) affects the kinematics of the hip, knee, and ankle joints, (2) promotes a more stable coordination at the left ankle, (3) affects interlimb coordination of the thighs, and (4) intralimb coordination between thigh and foot, (5) promotes greater dynamic stability of the hips, (6) increases the persistence of fluctuations in step length variability, and lastly (7) affects mechanical walking stability. These results support that transspinal stimulation is an important neuromodulatory strategy that directly affects gait symmetry and dynamic stability. The conservation of main effects at different frequencies and intensities calls for systematic investigation of stimulation protocols for clinical applications.

Soleus H-reflex amplitude modulation during walking remains physiological during transspinal stimulation in humans.

The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50Hz with 10kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50ms duration starting at 100ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.

Do long-lasting effects of epidural polarization of afferent fibres depend on persistent sodium current?

Few attempts have so far been made to define the mechanisms underlying the hour-long effects of trans-spinal stimulation combined with epidural polarization. In the present study, we investigated the potential involvement of non-inactivating sodium channels in afferent fibres. To this end, riluzole, a blocker of these channels, was administered locally to the dorsal columns close to the site of the excitation of afferent nerve fibres by epidural stimulation in deeply anaesthetized rats in vivo. Riluzole did not prevent the induction of the polarization-evoked sustained increase in the excitability of dorsal column fibres but tended to weaken it. It likewise weakened but did not abolish the sustained polarization-evoked shortening of the refractory period of these fibres. These results lead to the conclusion that the persistent sodium current may contribute to the sustained post-polarization-evoked effects but is only partly involved in both the induction and the expression of these effects.

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial

BackgroundThe seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown.MethodsForty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30 min of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30 min of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder, and sexual function are taken.DiscussionThe results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because, in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach.Trial registrationClinicalTrials.gov NCT04807764. Registered on March 19, 2021.

Optimization of Transspinal Stimulation Applications for Motor Recovery after Spinal Cord Injury: Scoping Review.

Spinal cord injury (SCI) is a debilitating condition that can significantly affect an individual's life, causing paralysis, autonomic dysreflexia, and chronic pain. Transspinal stimulation (TSS) is a non-invasive form of neuromodulation that activates the underlying neural circuitries of the spinal cord. Application of TSS can be performed through multiple stimulation protocols, which may vary in the electrodes' size or position as well as stimulation parameters, and which may influence the response of motor functions to the stimulation. Due to the novelty of TSS, it is beneficial to summarize the available evidence to identify the range of parameters that may provide the best outcomes for motor response. The PubMed and Google Scholar databases were searched for studies examining the effects of TSS on limb motor function. A literature search yielded 34 studies for analysis, in which electrode placement and stimulation parameters varied considerably. The stimulation protocols from each study and their impact on limb motor function were summarized. Electrode placement was variable based on the targeted limb. Studies for the upper limbs targeted the cervical enlargement with anatomical placement of the cathode over the cervical vertebral region. In lower-limb studies, the cathode(s) were placed over the thoracic and lumbar vertebral regions, to target the lumbar enlargement. The effects of carrier frequency were inconclusive across the studies. Multisite cathodal placements yielded favorable motor response results compared to single-site placement. This review briefly summarized the current mechanistic evidence of the effect of TSS on motor response after SCI. Our findings indicate that optimization of stimulation parameters will require future randomized controlled studies to independently assess the effects of different stimulation parameters under controlled circumstances.

Physiological effects of cathodal electrode configuration for transspinal stimulation in humans.

Transspinal stimulation modulates neuronal excitability and promotes recovery in upper motoneuron lesions. The recruitment input-output curves of transspinal evoked potentials (TEPs) recorded from knee and ankle muscles, and their susceptibility to spinal inhibition, were recorded when the position, size, and number of the cathode electrode were arranged in four settings or protocols (Ps). The four Ps were the following: 1) one rectangular electrode placed at midline (KNIKOU-LAB4Recovery or K-LAB4Recovery; P-KLAB), 2) one square electrode placed at midline (P-2), 3) two square electrodes 1 cm apart placed at midline (P-3), and 4) one square electrode placed on each paravertebral side (P-4). P-KLAB and P-3 required less current to reach TEP threshold or maximal amplitudes. A rightward shift in TEP recruitment curves was evident for P-4, whereas the slope was increased for P-2 and P-4 compared with P-KLAB and P-3. TEP depression upon single and paired transspinal stimuli was pronounced in ankle TEPs but was less prominent in knee TEPs. TEP depression induced by single transspinal stimuli at 1.0 Hz was similar for most TEPs across protocols, but TEP depression induced by paired transspinal stimuli was different between protocols and was replaced by facilitation at 100-ms interstimulus interval for P-4. Our results suggest that P-KLAB and P-3 are preferred based on excitability threshold of motoneurons. P-KLAB produced more TEP depression, thereby maximizing the engagement of spinal neuronal pathways. We recommend P-KLAB to study neurophysiological mechanisms underlying transspinal stimulation or when used as a neuromodulation method for recovery in neurological disorders.NEW & NOTEWORTHY Transspinal stimulation with a rectangular cathode electrode (P-KLAB) requires less current to produce transspinal evoked potentials and maximizes spinal inhibition. We recommend P-KLAB for neurophysiological studies or when used as a neuromodulation method to enhance motor output and normalize muscle tone in neurological disorders.

Brain and spinal cord paired stimulation coupled with locomotor training facilitates motor output in human spinal cord injury.

Combined interventions for neuromodulation leading to neurorecovery have gained great attention by researchers to resemble clinical rehabilitation approaches. In this randomized clinical trial, we established changes in the net output of motoneurons innervating multiple leg muscles during stepping when transcranial magnetic stimulation (TMS) of the primary motor cortex was paired with transcutaneous spinal (transspinal) stimulation over the thoracolumbar region during locomotor training. TMS was delivered before (TMS-transspinal) or after (transspinal-TMS) transspinal stimulation during the stance phase of the less impaired leg. Ten individuals with chronic incomplete or complete SCI received at least 20 sessions of training. Each session consisted of 240 paired stimuli delivered over 10-min blocks for 1 h during robotic assisted step training on a motorized treadmill. Body weight support, leg guidance force and treadmill speed were adjusted based on each subject's ability to step without knee buckling or toe dragging. Most transspinal evoked potentials (TEPs) recorded before and after each intervention from ankle and knee muscles during assisted stepping were modulated in a phase-dependent pattern. Transspinal-TMS and locomotor training affected motor neuron output of knee and ankle muscles with ankle TEPs to be modulated in a phase-dependent manner. TMS-transspinal and locomotor training increased motor neuron output for knee but not for ankle muscles. Our results support that targeted brain and spinal cord stimulation alters responsiveness of neurons over multiple spinal segments in people with chronic SCI. Noninvasive stimulation of the brain and spinal cord along with locomotor training is a novel neuromodulation method that can become a promising modality for rehabilitation in humans after SCI.

Brain and spinal cord paired stimulation coupled with locomotor training affects polysynaptic flexion reflex circuits in human spinal cord injury.

Neurorecovery from locomotor training is well established in human spinal cord injury (SCI). However, neurorecovery resulting from combined interventions has not been widely studied. In this randomized clinical trial, we established the tibialis anterior (TA) flexion reflex modulation pattern when transcranial magnetic stimulation (TMS) of the primary motor cortex was paired with transcutaneous spinal cord (transspinal) stimulation over the thoracolumbar region during assisted step training. Single pulses of TMS were delivered either before (TMS-transspinal) or after (transspinal-TMS) transspinal stimulation during the stance phase of the less impaired leg. Eight individuals with chronic incomplete or complete SCI received at least 20 sessions of paired stimulation during assisted step training. Each session consisted of 240 paired stimuli delivered over 10-min blocks for 1h during robotic-assisted step training with the Lokomat6 Pro®. Body weight support, leg guidance force and treadmill speed were adjusted based on each participant's ability to step without knee buckling or toe dragging. Both the early and late TA flexion reflex remained unaltered after TMS-transspinal and locomotor training. In contrast, the early and late TA flexion reflexes were significantly depressed during stepping after transspinal-TMS and locomotor training. Reflex changes occurred at similar slopes and intercepts before and after training. Our findings support that targeted brain and spinal cord stimulation coupled with locomotor training reorganizes the function of flexion reflex pathways, which are a part of locomotor networks, in humans with varying levels of sensorimotor function after SCI.Trial registration number NCT04624607; Registered on November 12, 2020.

Exoskeleton Training and Trans-Spinal Stimulation for Physical Activity Enhancement After Spinal Cord Injury (EXTra-SCI): An Exploratory Study.

After spinal cord injury (SCI) physical activity levels decrease drastically, leading to numerous secondary health complications. Exoskeleton-assisted walking (EAW) may be one way to improve physical activity for adults with SCI and potentially alleviate secondary health complications. The effects of EAW may be limited, however, since exoskeletons induce passive movement for users who cannot volitionally contribute to walking. Trans-spinal stimulation (TSS) has shown the potential to enable those with even the most severe SCI to actively contribute to movements during EAW. To explore the effects of EAW training on improving secondary health complications in persons with SCI, participants with chronic (n = 8) were enrolled in an EAW program 2–3 times per week for 12 weeks. Anthropometrics (seated and supine waist and abdominal circumferences (WC and AC), body composition assessment (dual exposure x-ray absorptiometry-derived body fat percent, lean mass and total mass for the total body, legs, and trunk), and peak oxygen consumption (VO2 during a 6-minute walk test [6MWT]) were assessed before and after 12 weeks of EAW training. A subset of participants (n = 3) completed EAW training with concurrent TSS, and neuromuscular activity of locomotor muscles was assessed during a 10-m walk test (10MWT) with and without TSS following 12 weeks of EAW training. Upon completion of 12 weeks of training, reductions from baseline (BL) were found in seated WC (−2.2%, P = 0.036), seated AC (−2.9%, P = 0.05), and supine AC (−3.9%, P = 0.017). Percent fat was also reduced from BL for the total body (−1.4%, P = 0.018), leg (−1.3%, P = 0.018), and trunk (−2%, P = 0.036) regions. No effects were found for peak VO2. The addition of TSS for three individuals yielded individualized responses but generally increased knee extensor activity during EAW. Two of three participants who received TSS were also able to initiate more steps without additional assistance from the exoskeleton during a 10MWT. In summary, 12 weeks of EAW training significantly attenuated markers of obesity relevant to cardiometabolic health in eight men with chronic SCI. Changes in VO2 and neuromuscular activity with vs. without TSS were highly individualized and yielded no overall group effects.

NAIAD-2020: Characteristics of Motor Evoked Potentials After 3-Day Exposure to Dry Immersion in Women.

As female astronauts participate in space flight more and more frequently, there is a demand for research on how the female body adapts to the microgravity environment. In particular, there is very little research on how the neuromuscular system reacts to gravitational unloading in women. We aimed to estimate changes in motor evoked potentials (MEPs) in the lower leg muscles in women after 3-day exposure to Dry Immersion (DI), which is one of the most widely used ground models of microgravity. Six healthy female volunteers (mean age 30.17 ± 5.5 years) with a natural menstrual cycle participated in this experiment. MEPs were recorded from the gastrocnemius and soleus muscles twice before DI, on the day of DI completion, and 3 days after DI, during the recovery period. To evoke motor responses, transcranial and trans-spinal magnetic stimulation was applied. We showed that changes in MEP characteristics after DI exposure were different depending on the stimulation site, but were similar for both muscles. For trans-spinal stimulation, MEP thresholds decreased compared to baseline values, and amplitudes, on the contrary, increased, resembling the phenomenon of hypogravitational hyperreflexia. This finding is in line with data observed in other experiments on both male and female participants. MEPs to transcranial stimulation had an opposing dynamic, which may have resulted from the small group size and large inter-subject variability, or from hormonal fluctuations during the menstrual cycle. Central motor conduction time remained unchanged, suggesting that pyramidal tract conductibility was not affected by DI exposure. More research is needed to explore the underlying mechanisms.

SY1.7. Rewiring pain through non-invasive brain stimulation

Chronic pain occurs when pain in an injured tissue persists beyond the normal recovery time. This crippling condition causes significant burden to the individual and to society. Despite years of research, treatments for chronic pain are largely ineffective, which may in part be due to a lack of understanding of the mechanisms that underpin chronic pain. There is increasing evidence that chronic musculoskeletal pain is associated with sensorimotor dysfunction, and that targeting the mechanisms associated with this dysfunction using non-invasive brain stimulation may alleviate symptoms of pain. This presentation will highlight studies investigating the manifestation of sensorimotor neuroplasticity in a range of musculoskeletal pain conditions such as low back pain, persistent elbow pain and persistent patellofemoral pain. These studies have used transcranial magnetic stimulation and electromyography methodologies and have shown that the organisation of the sensorimotor cortical representation of the pain afflicted muscle is altered. Novel treatment studies will then be reviewed. These studies have attempted to “rewire” pain by targeting sensorimotor cortical organisation using ‘top-down’ (non-invasive brain stimulation) and “bottom-up” approaches (trans-spinal stimulation, peripheral electrical stimulation and exercise). The potential limitations of these approaches will then be discussed including the large variation in responsiveness to treatment, and the need for individualized treatment. Indeed, our work using transitional pain models in healthy human subjects has shown that inter-individual differences in sensorimotor function in a pain free state and during persistent pain, can predict the severity of pain. It will be argued that tailoring treatment in accordance with an individual’s sensorimotor function in the early stages of pain may facilitate the diagnosis, prevention and treatment of pain. A planned project will be presented which will focus on modulating pain in accordance with these individual differences using non-invasive brain stimulation.

Transspinal stimulation and step training alter function of spinal networks in complete spinal cord injury.

Pilot study (case series). The objective of this study was to establish spinal neurophysiological changes following high-frequency transspinal stimulation during robot-assisted step training in individuals with chronic motor complete spinal cord injury (SCI). University research laboratory (Klab4Recovery). Four individuals with motor complete SCI received an average of 18 sessions of transspinal stimulation over the thoracolumbar region with a pulse train at 333 Hz during robotic-assisted step training. Each session lasted ~1 h, with an average of 240 stimulations delivered during each training session. Before and after the combined intervention, we evaluated the amplitude modulation of the long-latency tibialis anterior (TA) flexion reflex and transspinal evoked potentials (TEP) recorded from flexors and extensors during assisted stepping, and the TEP recruitment curves at rest. The long-latency TA flexion reflex was depressed in all phases of the step cycle and the phase-dependent amplitude modulation of TEPs was altered during assisted stepping, while spinal motor output based on TEP recruitment curves was increased after the combined intervention. This is the first study documenting noninvasive transspinal stimulation coupled with locomotor training depresses flexion reflex excitability and concomitantly increases motoneuron output over multiple spinal segments for both flexors and extensors in people with motor complete SCI. While both transspinal stimulation and locomotor training may act via similar activity-dependent neuroplasticity mechanisms, combined interventions for rehabilitation of neurological disorders has not been systematically assessed. Our current findings support locomotor training induced neuroplasticity may be augmented with transspinal stimulation.

Neurophysiological Changes After Paired Brain and Spinal Cord Stimulation Coupled With Locomotor Training in Human Spinal Cord Injury

Neurophysiological changes that involve activity-dependent neuroplasticity mechanisms via repeated stimulation and locomotor training are not commonly employed in research even though combination of interventions is a common clinical practice. In this randomized clinical trial, we established neurophysiological changes when transcranial magnetic stimulation (TMS) of the motor cortex was paired with transcutaneous thoracolumbar spinal (transspinal) stimulation in human spinal cord injury (SCI) delivered during locomotor training. We hypothesized that TMS delivered before transspinal (TMS-transspinal) stimulation promotes functional reorganization of spinal networks during stepping. In this protocol, TMS-induced corticospinal volleys arrive at the spinal cord at a sufficient time to interact with transspinal stimulation induced depolarization of alpha motoneurons over multiple spinal segments. We further hypothesized that TMS delivered after transspinal (transspinal-TMS) stimulation induces less pronounced effects. In this protocol, transspinal stimulation is delivered at time that allows transspinal stimulation induced action potentials to arrive at the motor cortex and affect descending motor volleys at the site of their origin. Fourteen individuals with motor incomplete and complete SCI participated in at least 25 sessions. Both stimulation protocols were delivered during the stance phase of the less impaired leg. Each training session consisted of 240 paired stimuli delivered over 10-min blocks. In transspinal-TMS, the left soleus H-reflex increased during the stance-phase and the right soleus H-reflex decreased at mid-swing. In TMS-transspinal no significant changes were found. When soleus H-reflexes were grouped based on the TMS-targeted limb, transspinal-TMS and locomotor training promoted H-reflex depression at swing phase, while TMS-transspinal and locomotor training resulted in facilitation of the soleus H-reflex at stance phase of the step cycle. Furthermore, both transspinal-TMS and TMS-transspinal paired-associative stimulation (PAS) and locomotor training promoted a more physiological modulation of motor activity and thus depolarization of motoneurons during assisted stepping. Our findings support that targeted non-invasive stimulation of corticospinal and spinal neuronal pathways coupled with locomotor training produce neurophysiological changes beneficial to stepping in humans with varying deficits of sensorimotor function after SCI.

Specific Features of the Motor Potentials of the Leg Muscles Induced by Magnetic Stimulation under the Conditions of a Five-Day \u201cDry\u201d Immersion in Healthy Volunteers

The aim of this study was to analyze the mechanisms of the development of hypogravitational hyperreflexia in the motoneuron pool of gravity-dependent muscles such as the gastrocnemius and soleus muscles of the leg under the conditions of five-day “dry” immersion in healthy volunteers using the method of transcranial and trans-spinal magnetic stimulation. The essence of the method lies in the stimulation of the areas of interest (motor areas of the cerebral cortex and lumbosacral thickening) with an electromagnetic stimulus. The study involved 10 subjects at the age of 29.9 ± 6.9 years, with no history of movement disorders or neurological diseases. The excitability of the motor neuron pool in both muscles was judged by the values of the thresholds and amplitudes of the motor response caused by transcranial and trans-spinal magnetic stimulations. A general pattern manifested in a significant decrease in thresholds and an increase in the amplitudes of motor responses caused by trans-spinal magnetic stimulation in both muscles gas been discovered. Specifically, the threshold of spinal evoked motor responses in both muscles decreased by 20%, and the amplitude increased by 150% after the end of immersion. The data obtained during the experiment confirm the spinal nature of the origin of hypogravitational hyperreflexia.

Neuronal Actions of Transspinal Stimulation on Locomotor Networks and Reflex Excitability During Walking in Humans With and Without Spinal Cord Injury.

This study investigated the neuromodulatory effects of transspinal stimulation on soleus H-reflex excitability and electromyographic (EMG) activity during stepping in humans with and without spinal cord injury (SCI). Thirteen able-bodied adults and 5 individuals with SCI participated in the study. EMG activity from both legs was determined for steps without, during, and after a single-pulse or pulse train transspinal stimulation delivered during stepping randomly at different phases of the step cycle. The soleus H-reflex was recorded in both subject groups under control conditions and following single-pulse transspinal stimulation at an individualized exactly similar positive and negative conditioning-test interval. The EMG activity was decreased in both subject groups at the steps during transspinal stimulation, while intralimb and interlimb coordination were altered only in SCI subjects. At the steps immediately after transspinal stimulation, the physiological phase-dependent EMG modulation pattern remained unaffected in able-bodied subjects. The conditioned soleus H-reflex was depressed throughout the step cycle in both subject groups. Transspinal stimulation modulated depolarization of motoneurons over multiple segments, limb coordination, and soleus H-reflex excitability during assisted stepping. The soleus H-reflex depression may be the result of complex spinal inhibitory interneuronal circuits activated by transspinal stimulation and collision between orthodromic and antidromic volleys in the peripheral mixed nerve. The soleus H-reflex depression by transspinal stimulation suggests a potential application for normalization of spinal reflex excitability after SCI.

Modulation of soleus H-reflex excitability following cervical transspinal conditioning stimulation in humans

The aim of this study was to establish the effects of transcutaneous spinal cord (transspinal) stimulation over the cervical region on soleus H-reflex excitability in healthy subjects while at rest. Reflex effects were established at subthreshold and suprathreshold cervical transspinal conditioning stimulation intensities of the extensor carpi radialis transspinal evoked potential. Twenty soleus H-reflexes at 0.125 Hz were recorded randomly under control conditions and following transspinal conditioning stimulation at conditioning-test intervals that ranged from 0 to 55 ms and tested in increment of 5 ms steps and at 100 ms. Cervical transspinal stimulation at suprathreshold and not at subthreshold intensities produced short, medium, and long-latency soleus H-reflex facilitation. The observed facilitatory reflex effects are consistent with activation of excitatory components of long propriospinal neurons. We propose the use of cervical transspinal stimulation to potentiate excitatory neuronal interactions between arms and legs in neurological disorders.

Transspinal stimulation downregulates activity of flexor locomotor networks during walking in humans

The objective of this study was to establish the effects of transspinal stimulation on short-latency tibialis anterior (TA) flexion reflex during walking in healthy humans. Single pulse transspinal stimulation was delivered at a conditioning-test (C-T) interval either after (~20 ms) or simultaneously with the last pulse of the pulse train (0 ms) delivered to the medial arch of the right foot. Transspinal stimulation was delivered at sub- and supra-threshold intensities of the spinally-mediated TA transspinal evoked potential. Stimulation was delivered randomly at different phases of the step cycle, based on the foot switch threshold signal, which was divided into 16 equal bins. The TA flexion reflex facilitation under control conditions occurred at heel contact and then progressively from late stance phase reaching its peak at early and late swing phases. Transspinal stimulation at a negative and suprathreshold 0 ms C-T interval depressed flexion reflex excitability at all phases of the step cycle. The short-latency TA flexion reflex depression was possibly mediated through spinal inhibitory interneurons acting at both pre- and post- motoneuronal sites or by transspinal stimulation affecting directly the activity of the flexor half spinal center. These results reveal direct actions of transspinal stimulation on human spinal locomotor networks.