Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury

Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). In this study, we established changes in the motoneuron output of individuals with and without SCI after repeated noninvasive transspinal stimulation at rest over the thoracolumbar enlargement, the spinal location of leg motor circuits. Cases of motor incomplete and complete SCI were included to delineate potential differences when corticospinal motor drive is minimal. All 10 SCI and 10 healthy control subjects received daily monophasic transspinal stimuli of 1-ms duration at 0.2 Hz at right soleus transspinal evoked potential (TEP) subthreshold and suprathreshold intensities at rest. Before and two days after cessation of transspinal stimulation, we determined changes in TEP recruitment input-output curves, TEP amplitude at stimulation frequencies of 0.1, 0.125, 0.2, 0.33 and 1.0 Hz, and TEP postactivation depression upon transspinal paired stimuli at interstimulus intervals of 60, 100, 300, and 500 ms. TEPs were recorded at rest from bilateral ankle and knee flexor/extensor muscles. Repeated transspinal stimulation increased the motoneuron output over multiple segments. In control and complete SCI subjects, motoneuron output increased for knee muscles, while in motor incomplete SCI subjects motoneuron output increased for both ankle and knee muscles. In control subjects, TEPs homosynaptic and postactivation depression were present at baseline, and were potentiated for the distal ankle or knee flexor muscles. TEPs homosynaptic and postactivation depression at baseline depended on the completeness of the SCI, with minimal changes observed after transspinal stimulation. These results indicate that repeated transspinal stimulation increases spinal motoneuron responsiveness of ankle and knee muscles in the injured human spinal cord, and thus can promote motor recovery. This noninvasive neuromodulation method is a promising modality for promoting functional neuroplasticity after SCI

Transspinal Direct Current Stimulation Produces Persistent Plasticity in Human Motor Pathways

The spinal cord is an integration center for descending, ascending, and segmental neural signals. Noninvasive transspinal stimulation may thus constitute an effective method for concomitant modulation of local and distal neural circuits. In this study, we established changes in cortical excitability and input/output function of corticospinal and spinal neural circuits before, at 0–15 and at 30–45 minutes after cathodal, anodal, and sham transspinal direct current stimulation (tsDCS) to the thoracic region in healthy individuals. We found that intracortical inhibition was different among stimulation polarities, however remained unchanged over time. Intracortical facilitation increased after cathodal and anodal tsDCS delivered with subjects seated, and decreased after cathodal tsDCS delivered with subjects lying supine. Both cathodal and anodal tsDCS increased corticospinal excitability, yet facilitation was larger and persisted for 30 minutes post stimulation only when cathodal tsDCS was delivered with subjects lying supine. Spinal input/output reflex function was decreased by cathodal and not anodal tsDCS. These changes may be attributed to altered spontaneous neural activity and membrane potentials of corticomotoneuronal cells by tsDCS involving similar mechanisms to those mediating motor learning. Our findings indicate that thoracic tsDCS has the ability to concomitantly alter cortical, corticospinal, and spinal motor output in humans

Editorial: Advances in Invasive and Non-invasive Brain Stimulation for Dystonia and Other Hyperkinetic Movement Disorders

No abstract availabl

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle activation profiles are observed during locomotion across species. This difference may potentially be driven by a modified distribution of muscle afferents at multiple segmental levels in humans, resulting in an altered interaction between different classes of spinal interneurons. Further, different classes of spinal interneurons are likely activated or silent to some extent simultaneously in all species. Regardless of these limitations, continuous efforts on the function of spinal interneuronal circuits during mammalian locomotion will assist in delineating the neural mechanisms underlying locomotor control, and help develop novel targeted rehabilitation strategies in cases of impaired bipedal gait in humans. These rehabilitation strategies will include activity-based therapies and targeted neuromodulation of spinal interneuronal circuits via repetitive stimulation delivered to the brain and/or spinal cord

Remodeling Brain Activity by Repetitive Cervicothoracic Transspinal Stimulation after Human Spinal Cord Injury

Interventions that can produce targeted brain plasticity after human spinal cord injury (SCI) are needed for restoration of impaired movement in these patients. In this study, we tested the effects of repetitive cervicothoracic transspinal stimulation in one person with cervical motor incomplete SCI on cortical and corticospinal excitability, which were assessed via transcranial magnetic stimulation with paired and single pulses, respectively. We found that repetitive cervicothoracic transspinal stimulation potentiated intracortical facilitation in flexor and extensor wrist muscles, recovered intracortical inhibition in the more impaired wrist flexor muscle, increased corticospinal excitability bilaterally, and improved voluntary muscle strength. These effects may have been mediated by improvements in cortical integration of ascending sensory inputs and strengthening of corticospinal connections. Our novel therapeutic intervention opens new avenues for targeted brain neuromodulation protocols in individuals with cervical motor incomplete SCI

Cortical and Subcortical Contributions to Neuroplasticity after Repetitive Transspinal Stimulation in Humans

The objectives of this study were to establish cortical and subcortical contributions to neuroplasticity induced by noninvasive repetitive transspinal stimulation in human subjects free of any neurological disorder. To meet our objectives, before and after 40 minutes of transspinal stimulation we established changes in tibialis anterior (TA) motor-evoked potentials (MEPs) in response to paired transcranial magnetic stimulation (TMS) pulses at interstimulus intervals (ISIs) consistent with I-wave periodicity. In order to establish to what extent similar actions are exerted at the spinal cord and motor axons, changes in soleus H-reflex and transspinal evoked potential (TEP) amplitude following transspinal and group Ia afferent conditioning stimulation, respectively, were established. After 40 min of transspinal stimulation, the TA MEP consecutive peaks of facilitation produced by paired TMS pulses were significantly decreased supporting for depression of I-waves. Additionally, the soleus H-reflex and ankle TEP depression following transspinal and group Ia afferent conditioning stimulation was potentiated at intervals when both responses interacted at the spinal cord and nerve axons. These findings support the notion that repetitive transspinal stimulation decreases corticocortical inputs onto corticospinal neurons and promotes a surround inhibition in the spinal cord and nerve axons. This novel method may be a suitable neuromodulation tool to alter excitability at cortical and subcortical levels in neurological disorders

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle activation profiles are observed during locomotion across species. This difference may potentially be driven by a modified distribution of muscle afferents at multiple segmental levels in humans, resulting in an altered interaction between different classes of spinal interneurons. Further, different classes of spinal interneurons are likely activated or silent to some extent simultaneously in all species. Regardless of these limitations, continuous efforts on the function of spinal interneuronal circuits during mammalian locomotion will assist in delineating the neural mechanisms underlying locomotor control, and help develop novel targeted rehabilitation strategies in cases of impaired bipedal gait in humans. These rehabilitation strategies will include activity-based therapies and targeted neuromodulation of spinal interneuronal circuits via repetitive stimulation delivered to the brain and/or spinal cord

Short-term locomotor adaptation to a robotic ankle exoskeleton does not alter soleus Hoffmann reflex amplitude

<p>Abstract</p> <p>Background</p> <p>To improve design of robotic lower limb exoskeletons for gait rehabilitation, it is critical to identify neural mechanisms that govern locomotor adaptation to robotic assistance. Previously, we demonstrated soleus muscle recruitment decreased by ~35% when walking with a pneumatically-powered ankle exoskeleton providing plantar flexor torque under soleus proportional myoelectric control. Since a substantial portion of soleus activation during walking results from the stretch reflex, increased reflex inhibition is one potential mechanism for reducing soleus recruitment when walking with exoskeleton assistance. This is clinically relevant because many neurologically impaired populations have hyperactive stretch reflexes and training to reduce the reflexes could lead to substantial improvements in their motor ability. The purpose of this study was to quantify soleus Hoffmann (H-) reflex responses during powered versus unpowered walking.</p> <p>Methods</p> <p>We tested soleus H-reflex responses in neurologically intact subjects (n=8) that had trained walking with the soleus controlled robotic ankle exoskeleton. Soleus H-reflex was tested at the mid and late stance while subjects walked with the exoskeleton on the treadmill at 1.25 m/s, first without power (first unpowered), then with power (powered), and finally without power again (second unpowered). We also collected joint kinematics and electromyography.</p> <p>Results</p> <p>When the robotic plantar flexor torque was provided, subjects walked with lower soleus electromyographic (EMG) activation (27-48%) and had concomitant reductions in H-reflex amplitude (12-24%) compared to the first unpowered condition. The H-reflex amplitude in proportion to the background soleus EMG during powered walking was not significantly different from the two unpowered conditions.</p> <p>Conclusion</p> <p>These findings suggest that the nervous system does not inhibit the soleus H-reflex in response to short-term adaption to exoskeleton assistance. Future studies should determine if the findings also apply to long-term adaption to the exoskeleton.</p

Dipolar cortico-muscular electrical stimulation: a novel method that enhances motor function in both - normal and spinal cord injured mice

<p>Abstract</p> <p>Background</p> <p>Electrical stimulation of the central and peripheral nervous systems is a common tool that is used to improve functional recovery after neuronal injury.</p> <p>Methods</p> <p>Here we described a new configuration of electrical stimulation as it was tested in anesthetized control and spinal cord injury (SCI) mice. Constant voltage output was delivered through two electrodes. While the negative voltage output (ranging from -1.8 to -2.6 V) was delivered to the muscle via transverse wire electrodes (diameter, 500 μm) located at opposite ends of the muscle, the positive output (ranging from + 2.4 to +3.2 V) was delivered to the primary motor cortex (M1) (electrode tip, 100 μm). The configuration was named dipolar cortico-muscular stimulation (dCMS) and consisted of 100 pulses (1 ms pulse duration, 1 Hz frequency).</p> <p>Results</p> <p>In SCI animals, after dCMS, cortically-elicited muscle contraction improved markedly at the contralateral (456%) and ipsilateral (457%) gastrocnemius muscles. The improvement persisted for the duration of the experiment (60 min). The enhancement of cortically-elicited muscle contraction was accompanied by the reduction of M1 maximal threshold and the potentiation of spinal motoneuronal evoked responses at the contralateral (313%) and ipsilateral (292%) sides of the spinal cord. Moreover, spontaneous activity recorded from single spinal motoneurons was substantially increased contralaterally (121%) and ipsilaterally (54%). Interestingly, spinal motoneuronal responses and muscle twitches evoked by the test stimulation of non-treated M1 (received no dCMS) were significantly enhanced as well. Similar results obtained from normal animals albeit the changes were relatively smaller.</p> <p>Conclusion</p> <p>These findings demonstrated that dCMS could improve functionality of corticomotoneuronal pathway and thus it may have therapeutic potential.</p

Repeatability of Corticospinal and Spinal Measures during Lengthening and Shortening Contractions in the Human Tibialis Anterior Muscle

Elements of the human central nervous system (CNS) constantly oscillate. In addition, there are also methodological factors and changes in muscle mechanics during dynamic muscle contractions that threaten the stability and consistency of transcranial magnetic stimulation (TMS) and perpherial nerve stimulation (PNS) measures