V. A. Selionov

Tonic central and sensory stimuli facilitate involuntary air-stepping in humans

Air-stepping can be used as a model for investigating rhythmogenesis and its interaction with sensory input. Here we show that it is possible to entrain involuntary rhythmic movement patterns in healthy humans by using different kinds of stimulation techniques. The subjects lay on their sides with one or both legs suspended, allowing low-friction horizontal rotation of the limb joints. To evoke involuntary stepping of the suspended leg, either we used continuous muscle vibration, electrical stimulation of the superficial peroneal or sural nerves, the Jendrassik maneuver, or we exploited the postcontraction state of neuronal networks (Kohnstamm phenomenon). The common feature across all stimulations was that they were tonic. Air-stepping could be elicited by most techniques in about 50% of subjects and involved prominent movements at the hip and the knee joint (approximately 40-70 degrees). Typically, however, the ankle joint was not involved. Minimal loading forces (4-25 N) applied constantly to the sole (using a long elastic cord) induced noticeable (approximately 5-20 degrees) ankle-joint-angle movements. The aftereffect of a voluntary long-lasting (30-s) contraction in the leg muscles featured alternating rhythmic leg movements that lasted for about 20-40 s, corresponding roughly to a typical duration of the postcontraction activity in static conditions. The Jendrassik maneuver per se did not evoke air-stepping. Nevertheless, it significantly prolonged rhythmic leg movements initiated manually by an experimenter or by a short (5-s) period of muscle vibration. Air-stepping of one leg could be evoked in both forward and backward directions with frequent spontaneous transitions, whereas involuntary alternating two-legged movements were more stable (no transitions). The hypothetical role of tonic influences, contact forces, and bilateral coordination in rhythmogenesis is discussed. The results overall demonstrated that nonspecific tonic drive may cause air-stepping and the characteristics and stability of the evoked pattern depended on the sensory input.

Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans

The mammalian lumbar spinal cord has the capability to generate locomotor activity in the absence of input from the brain. Previously, we reported that transcutaneous electrical stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in noninjured subjects when their legs are placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46-56, 2012). In the present study we hypothesized that stimulating multiple spinal sites and therefore unique combinations of networks converging on postural and locomotor lumbosacral networks would be more effective in inducing more robust locomotor behavior and more selective control than stimulation of more restricted networks. We demonstrate that simultaneous stimulation at the cervical, thoracic, and lumbar levels induced coordinated stepping movements with a greater range of motion at multiple joints in five of six noninjured subjects. We show that the addition of stimulation at L1 and/or at C5 to stimulation at T11 immediately resulted in enhancing the kinematics and interlimb coordination as well as the EMG patterns in proximal and distal leg muscles. Sequential cessation of stimulation at C5 and then at L1 resulted in a progressive degradation of the stepping pattern. The synergistic and interactive effects of transcutaneous stimulation suggest a multisegmental convergence of descending and ascending, and most likely propriospinal, influences on the spinal neuronal circuitries associated with locomotor activity. The potential impact of using multisite spinal cord stimulation as a strategy to neuromodulate the spinal circuitry has significant implications in furthering our understanding of the mechanisms controlling posture and locomotion and for regaining significant sensorimotor function even after a severe spinal cord injury.

Human cervical spinal cord circuitry activated by tonic input can generate rhythmic arm movements.

The coordination between arms and legs during human locomotion shares many features with that in quadrupeds, yet there is limited evidence for the central pattern generator for the upper limbs in humans. Here we investigated whether different types of tonic stimulation, previously used for eliciting stepping-like leg movements, may evoke nonvoluntary rhythmic arm movements. Twenty healthy subjects participated in this study. The subject was lying on the side, the trunk was fixed, and all four limbs were suspended in a gravity neutral position, allowing unrestricted low-friction limb movements in the horizontal plane. The results showed that peripheral sensory stimulation (continuous muscle vibration) and central tonic activation (postcontraction state of neuronal networks following a long-lasting isometric voluntary effort, Kohnstamm phenomenon) could evoke nonvoluntary rhythmic arm movements in most subjects. In ∼40% of subjects, tonic stimulation elicited nonvoluntary rhythmic arm movements together with rhythmic movements of suspended legs. The fact that not all participants exhibited nonvoluntary limb oscillations may reflect interindividual differences in responsiveness of spinal pattern generation circuitry to its activation. The occurrence and the characteristics of induced movements highlight the rhythmogenesis capacity of cervical neuronal circuitries, complementing the growing body of work on the quadrupedal nature of human gait.

Lack of non-voluntary stepping responses in Parkinson's disease.

The majority of research and therapeutic actions in Parkinsons disease (PD) focus on the encephalic areas, however, the potential involvement of the spinal cord in its genesis has received little attention. Here we examined spinal locomotor circuitry activation in patients with PD using various types of central and peripheral tonic stimulation and compared results to those of age-matched controls. Subjects lay on their sides with both legs suspended, allowing low-friction horizontal rotation of the limb joints. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by the absence of external resistance. In contrast to the frequent occurrence of non-voluntary stepping responses in healthy subjects, both peripheral (muscle vibration) and central (Jendrassik maneuver, mental task, Kohnstamm phenomenon) tonic influences had little if any effect on rhythmic leg responses in PD. On the other hand, a remarkable feature of voluntary air-stepping movements in patients was a significantly higher frequency of leg oscillations than in age-matched controls. A lack of non-voluntary stepping responses was also observed after dopaminergic treatment despite the presence of prominent shortening reactions (SRs) to passive movements. We argue that the state and the rhythmogenesis capacity of the spinal circuitry are impaired in patients with PD. In particular, the results suggest impaired central pattern generator (CPG) access by sensory and central activations.

Transcutaneous electrical stimulation of the spinal cord: A noninvasive tool for the activation of stepping pattern generators in humans

A new method for the activation of spinal locomotor networks (SLN) in humans by transcutaneous electrical spinal cord stimulation (tESCS) has been described. The tESCS applied in the region of the T11-T12 vertebrae with a frequency of 5–40 Hz elicited involuntary step-like movements in healthy subjects with their legs suspended in a gravity-neutral position. The amplitude of evoked step-like movements increased with increasing tESCS frequency. The frequency of evoked step-like movements did not depend on the frequency of tESCS. It was shown that the hip, knee, and ankle joints were involved in the evoked movements. It has been suggested that tESCS activates the SPG (SLN) through in part, via the dorsal roots that enter the spinal cord. tESCS can be used as a noninvasive method in rehabilitation of spinal pathology.

Effects of transcranial magnetic stimulation during voluntary and non-voluntary stepping movements in humans

Here, we compared motor evoked potentials (MEP) in response to transcranial magnetic stimulation of the motor cortex and the H-reflex during voluntary and vibration-induced air-stepping movements in humans. Both the MEPs (in mm biceps femoris, rectus femoris and tibialis anterior) and H-reflex (in m soleus) were significantly smaller during vibration-induced cyclic leg movements at matched amplitudes of angular motion and muscle activity. These findings highlight differences between voluntary and non-voluntary activation of the spinal pattern generator circuitry in humans, presumably due to an extra facilitatory effect of voluntary control/triggering of stepping on spinal motoneurons and interneurons. The results support the idea of active engagement of supraspinal motor areas in developing central pattern generator-modulating therapies.

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion.

Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

An ability to produce rhythmic activity is ubiquitous for locomotor pattern generation and modulation. The role that the rhythmogenesis capacity of the spinal cord plays in injured populations has become an area of interest and systematic investigation among researchers in recent years, despite its importance being long recognized by neurophysiologists and clinicians. Given that each individual interneuron, as a rule, receives a broad convergence of various supraspinal and sensory inputs and may contribute to a vast repertoire of motor actions, the importance of assessing the functional state of the spinal locomotor circuits becomes increasingly evident. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by a reduction of external resistance. This article aims to provide a review on current issues related to the “locomotor” state and interactions between spinal and supraspinal influences on the central pattern generator (CPG) circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries.

Integration of sensory, spinal, and volitional descending inputs in regulation of human locomotion

We reported previously that both transcutaneous electrical spinal cord stimulation and direct pressure stimulation of the plantar surfaces of the feet can elicit rhythmic involuntary step-like movements in noninjured subjects with their legs in a gravity-neutral apparatus. The present experiments investigated the convergence of spinal and plantar pressure stimulation and voluntary effort in the activation of locomotor movements in uninjured subjects under full body weight support in a vertical position. For all conditions, leg movements were analyzed using electromyographic (EMG) recordings and optical motion capture of joint kinematics. Spinal cord stimulation elicited rhythmic hip and knee flexion movements accompanied by EMG bursting activity in the hamstrings of 6/6 subjects. Similarly, plantar stimulation induced bursting EMG activity in the ankle flexor and extensor muscles in 5/6 subjects. Moreover, the combination of spinal and plantar stimulation exhibited a synergistic effect in all six subjects, eliciting greater motor responses than either modality alone. While the motor responses to spinal vs. plantar stimulation seems to activate distinct but overlapping spinal neural networks, when engaged simultaneously, the stepping responses were functionally complementary. As observed during induced (involuntary) stepping, the most significant modulation of voluntary stepping occurred in response to the combination of spinal and plantar stimulation. In light of the known automaticity and plasticity of spinal networks in absence of supraspinal input, these findings support the hypothesis that spinal and plantar stimulation may be effective tools for enhancing the recovery of motor control in individuals with neurological injuries and disorders.

Mechanical stimulation of the support zones of soles: The method of noninvasive activation of the stepping movement generators in humans

The effects of mechanical stimulation of the soles’ support zones in the modes of slow and fast walking (75 and 120 steps per minute) were studied using the model of supportlessness (legs suspension). 20 healthy subjects participated in the study. EMG activity of hip and shin muscles was recorded. Kinematics of leg movements was assessed with the use of videoanalysis system. In 80% of cases support stimulation was followed by leg movements, in 69% of which they had characteristics of locomotions being accompanied by the burst-like electromyographic activities. The order of involvement of leg muscles and organization of antagonistic muscles activities were analogous to those of voluntary walking. The latencies of electromyographic activity in hip and shin muscles composed 5.17 ± 1.08 and 14.01 ± 2.82 s, respectively, the frequencies of bursts differed significantly depending on stimulation frequency. In 31% of cases the electromyographical activity following the stimulation of the soles’ support zones had not burst-like but uninterrupted pattern. Its amplitude rose smoothly reaching a certain level that was subsequently maintained. Results of the study showed that soles’ support zones stimulation in the mode of locomotion could activate a locomotor generator provoking the appearance of locomotion-like activity and that effect evoked by this stimulation includes not only rhythmical but also non-rhythmical (probably postural) components of walking.