Synergistic influences of sensory and central stimuli on non-voluntary rhythmic arm movements.

In recent years, neuromodulation of the cervical spinal circuitry has become an area of interest for investigating rhythmogenesis of the human spinal cord and interaction between cervical and lumbosacral circuitries, given the involvement of rhythmic arm muscle activity in many locomotor tasks. We have previously shown that arm muscle vibrostimulation can elicit non-voluntary upper limb oscillations in unloading body conditions. Here we investigated the excitability of the cervical spinal circuitry by applying different peripheral and central stimuli in healthy humans. The rationale for applying combined stimuli is that the efficiency of only one stimulus is generally limited. We found that low-intensity electrical stimulation of the superficial arm median nerve can evoke rhythmic arm movements. Furthermore, the movements were enhanced by additional peripheral stimuli (e.g., arm muscle vibration, head turns or passive rhythmic leg movements). Finally, low-frequency transcranial magnetic stimulation of the motor cortex significantly facilitated rhythmogenesis. The findings are discussed in the general framework of a brain-spinal interface for developing adaptive central pattern generator-modulating therapies.

[The Activation of Interlimb Interactions Increase the Motor Output in Legs in Healthy Subjects under the Conditions of Arm and Leg Unloading].

We studied the effect of arm movements and movements of separate arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration-triggered stepping-like leg movements under the conditions of horizontal support of upper and lower limbs. The horizontal support of arms provided a significantly increase in the rate of activation of locomotor automatism by non-invasive impact on tonic sensory inputs. The addition of active arm movements during involuntary rhytmic stepping-like leg movements led to an increase in EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. Passive arm movements had the same effect on induced leg movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and an increase in the amplitude of movements of the knee and hip joints. At the same time, the movement of forearms. and wrists had similar facilitating effect on electrophysiological and kinematic characteristics of rhytmic stepping-like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of sub-threshold vibration of leg muscles, voluntary arm movements led to the activation of involuntary rhytmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhytmic stepping than during involuntary leg movements. Thus, the simultaneous movements of upper and lower limbs are an effective method of activation of neural networks connecting the rhythm generators of arms and legs. Under the conditions of arm and leg unloading, the interactions between the cervical and lumbosacral segments of the spinal cord seem to play the major role in the impact of arm movements on the patterns of leg movements. The described methods of activation of interlimb interactions can be used in the rehabilitation of post-stroke patients and patients with spinal cord injuries, Parkinson's disease and other neurological diseases.

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.

[Are Interlimb Interactions Disturbed in Patients with Parkinson's Disease: a Study in Unloading Condition?]

During natural human locomotion neural connections characteristic for the control of quadrupedal walking are activated. The degree of interaction between the neural networks generating rhythmic movements of the upper and lower extremities, depends on the tonic state of each of these networks, adjustable by motor command in the brain. The distortion of such command in patients with Parkinson's disease (PD) may lead to disturbance of interlimb interactions. In conditions of arms and legs unloading in 17 patients with PD and 16 healthy subjects investigated the effect of limb movement of one girdle on the parameters of motor activity of the limbs of the other girdle in their combined cyclic movements. In patients the weakening of influences of active or passive arm movements, and active movements of the distal parts of the arms on voluntary leg movements was shown, while in healthy subjects the effect of arm movements on the parameters of voluntary movements was significant. The effect of arm movements on the possibility of involuntary activation of air- stepping by vibratory stimulation of the leg muscles in patients was absent, while in healthy subjects the motor activity of the arms increased the opportunity of involuntary rhythm activation. The differences in the influence of leg movements to the rhythmic movement of the upper extremities in patients and healthy subjects were revealed. The medication exhibited interlimb interaction, but it was insufficient for normalization of the state of neural networks in patients. It is concluded that in patients with PD, neural networks generating stepping rhythm are in a state of heightened tonic activity. This does not allow not only activating involuntary rhythmic movements, but also showing facilitation effect with arms to legs.

[Investigation of muscle tone in patients with Parkinson's disease in unloading conditions].

Parkinson's disease (PD) is a progressive neurodegenerative disorder, ones of the main symptoms of which are hypertonicity and emergent difficulties during performance of stepping movements due to increased muscle stiffness. Biomechanical (stiffness) and electrophysiological (shorting reaction) characteristics of hip and shank muscles were examined in 25 patients with mild and moderate stages of PD (1 to 3 of Hoehn & Yahr Rating Scale, 61 +/- 9 years) and 22 age-matched healthy controls in unloading leg conditions during passive flexion/extension of hip, knee and ankle joints, as well as the changes of tonic state under levodopa influence. The data obtained were compared with similar findings of healthy subjects. Essentially greater stiffness in all leg muscle groups (with the exception of foot extensors) were observed in patients as compared with healthy. During passive movements the shorting reactions (SR) in hip and shank muscles were often observed, in healthy subjects the SR were observed more rarely. In patients with PD the values of SR in extensors of hip and shank, as well as in flexor and extensor muscles of foot were essentially greater then in healthy. The medicine essentially reduced the stiffness of hip flexors and flexors and foot extensors. The SR were persisted but the frequency of its appearance was decreased in half of investigated muscles, and significant decreasing of SR amount was observed in extensors of foot. The medicine did not exert influence upon SR in proximal muscles. Thus, increasing muscle stiffness in patients with PD is manifested in uncorrected reactions on external disturbances and reflected in increasing of reflectory reaction of muscles.

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.

[Interlimb interactions during cyclic in-phase and antiphased movements of arms and legs and their dependence on afferent influences].

Coordinated movements of arms and legs suppose the neural interaction between the generators of the rhythmics of the upper and lower extremities. In the lying position in 10 healthy subjects activity of the muscles of the upper and lower extremities was recorded when separate and joint cyclic movements of the arms and legs with different phase relationships between the movements of the limbs were performed, and under various conditions of the motor task. Antiphased active arm movements were characterized by increased muscle activity than during in-phase mode. The activity of the arm muscles under passive movements, imposed by experimenter, was significantly less than their activity when passive movements of the arms were imposed by the other arm. When loading one arm the muscle activity in the other passively moving arm increased independently from the synergy of arm movements. During motor tasks, implementing joint antiphased movements as the upper and lower extremities, compared to motor task, implementing their joint in-phase movements, there has been a significant increase in activity in the biceps brahii muscle, the tibialis anterior muscle and biceps femoris muscle. Loading of arms in these motor tasks has been accompanied by increased activity in some of the leg muscles. Increasing of frequency of rhythmic movements resulted in a significant growth of the muscle activity of the arms and legs with their cooperative movements with greater rate of rise of flexor muscles activity for arms and legs during joint antiphased movements. Thus, the spatial organization of movements and kind of afferent influences are significant factors of interlimb interaction, which, in turn, determine the type of neural interconnections that are involved in the regulation of movements.

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

The majority of research and therapeutic actions in Parkinson's 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.

[Mechanical stimulation of soles' support zones: non-invasive method of activation of generators of stepping movements in man].

The effects of mechanical stimulation of the soles' support zones in regimens of slow and fastwalking (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. Kinematic of leg movements was assessed with the use of videoanalysis system. Support stimulation was followed by leg movements in 80% of cases, in 53% it was a locomotion-like movement. EMG bursts accompanied the movements. Involvement order and alteration of bursts in muscles were similar to voluntary walking. EMG activity occurred with a delay of 5.17 ± 1.08 seconds for hip muscles and 14.01 ± 2.82 seconds for shin muscles, frequency of bursts differed from stimulation frequency. Support stimulation was followed by leg movements in 80% of cases, in 53% of which they had characteristics of locomotions being accompanied by the burst-like electromyographic activities. Involvement order of the leg muscles and organization of antagonistic muscles activities were analogous to that of voluntary walking. The latencies of electromyographic activity in hip muscles composed 5.17 ± 1.083 s and 14.01 ± 2.82 s - for shin muscles, frequency of bursts differed significantly from stimulation frequency. In 31% of cases the electromyographical activity following the stimulation of the soles' support zones was not burst-like. Its amplitude rose smoothly reaching a certain level that was subsequently maintained. Results of the study showed that soles' support zones stimulation in regimen of locomotion can activate a locomotor generator and that effect evoked by this stimulation includes not only rhythmical but also non-rhythmical (probably postural) components of walking.

[Abnormalities in mutual influences of upper and lower limbs in patients with stroke].

Previously, in healthy subjects the common pattern of muscle activation and specifics of interlimb neuron connections during performance of rhythmic separate and simultaneous movements of arms and legs in the lying position, which reflect functional meaningful of interlimb interactions, were shown. The aim of this research was to investigate such mutual influences of upper and lower limbs during the execution of similar motor tasks by patients with stroke. In sixteen poststroke patients with different stage of hemiparesis arms movements together with or without legs movements were performed, while lying supine. It was demonstrated that the common pattern of muscle activity distribution under the execution of voluntary cyclic movements by both arms was disordered. Passive rhythmic movements of each arm caused the phased EMG activity in shoulder muscles in patients with mild hemiparesis, but no activation was observed in patients with severe paresis. The loading of nonparetic arm resulted in an increasing of activity in shoulder flexor muscles of paretic arm in patients with weak paresis (which was typical for healthy subjects), while it not exerted essential influences in patients with severe paresis. Under connecting the cyclic movements of arms with stepping movements of legs in diagonal synergy the activity in proximal muscles of both arms was decreased irrespective of the paresis degree, as it was seeing in healthy subjects. Simultaneous arms and legs movements did not change the muscle activity in non-paretic leg in both groups of patients, but in some muscles of paretic leg the activity even decreased. The results obtained revealed important features of poststroke motor disturbances, which caused the changes of interlimb interaction and in great degree depended on the level of paresis. The data of investigation can be of a great importance for developing the new methods for rehabilitative procedure in patients with stroke.

[Transcutaneous electrical stimulation of the spinal cord: non-invasive tool for activation of locomotor circuitry in human].

A new tool for locomotor circuitry activation in the non-injured human by transcutaneous electrical spinal cord stimulation (tSCS) has been described. We show that continuous tSCS over T11-T12 vertebrae at 5-40 Hz induced involuntary locomotor-like stepping movements in subjects with their legs in a gravity-independent position. The increase of frequency of tSCS from 5 to 30 Hz augmented the amplitude of evoked stepping movements. The duration of cycle period did not depend on frequency of tSCS. During tSCS the hip, knee and ankle joints were involved in the stepping performance. It has been suggested that tSCS activates the locomotor circuitry through the dorsal roots. It appears that tSCS can be used as a non-invasive method in rehabilitation of spinal pathology.

[The influence of vibration on spinal alpha-motoneurons excitability in static conditions and during evoked stepping in human].

In healthy human the excitability of spinal alpha-motoneurons under application of vibrostimulation (20-60 Hz) to different leg muscles was investigated both in stationary condition and during stepping movements caused by vibration in the condition of suspended leg. In 15 subjects the amplitude of H-reflex were compared under vibration of rectus femoris (RF) and biceps femoris (BF) muscles of left leg as well during vibration of rectus femoris of contralateral, motionless leg in three spatial positions: upright, supine and on right side of body with suspended left leg. In dynamic conditions the amount of H-reflex was compared during evoked and voluntary stepping at 8 intervals of step cycle. In all body positions the vibration of each ipsilateral leg muscles caused significant suppression of H-reflex, this suppression was more prominent in the air-stepping conditions. The vibration of contralateral leg RF muscle had a weak influence on the amplitude of H-reflex. In 7 subjects the muscle vibration of ipsilateral and contralateral legs generated stepping movements. During evoked "air-stepping" H-reflex had different amplitudes in different phases of step cycle. At the same time the differences between responses under voluntary and non-voluntary stepping were revealed only in stance phase. Thus, different degree of H-reflex suppression by vibration under different body position in space depends on, it seems to be, from summary afferent inflows to spinal cord interneurons, which participate in regulation of posture and locomotion. Seemingly, the increasing of spinal cord neurons excitability occurs under involuntary air-stepping in swing phase, which is necessary for activation of locomotor automatism under unloading leg conditions.

[Mutual influences of upper and lower extrimities during cyclic movements].

The possibility of muscle activation of passive arm during its cyclic movements, imposed by active movements of contralateral arm or by experimenter was studied, as well as the influence of lower extremities cyclic movements onto arm muscles activity. In addition to that the activity of legs muscles was estimated in dependence on motor task condition for arms. Ten healthy supine subjects carried out opposite movements of arms with and without stepping-like movements of both legs. The experiment included three conditions for arm movements: 1) the active movements of both arms; 2) the active movements of one arm, when other entirely passive arm participated in the movement by force; 3) passive arm movement caused by experimenter. In the condition 2) additional load on active arm was applied (30 N and 60 N). In all three conditions the experiment was carried out with arms movements only or together with legs movements. The capability of passive moving arm muscles activation depended on increasing afferent inflow from muscles of contralateral arm was demonstrated. Emerging electrical activity was modulated in the arms movements cycle and depended on the degree of active arm loading. During combined active movements of arms and legs the reduction of activity in the flexor muscles of shoulder and forearm was observed. Concomitant arms movements increased the magnitude ofelectromiographic bursts during passive stepping-like movements in the most of recorded muscles, and the same increasing was only observed in biceps femoris and tibialis anterior muscles during active legs movement. The increasing of loading of one arm caused essential augmentation of EMG-activity in the majority of recording legs muscles. The data obtained are the additional proof of existence of functionally significant neuronal interaction both between arms and between upper and lower extremities, which is evidently depend on the intraspinal neuronal connections.

[The influence of afferent inputs from the foot load receptors onto spinal alpha-motoneurons excitability in air-stepping condition].

We investigated excitability of alpha-motoneurons during voluntary and passive locomotor-like movements under air-stepping conditions during the imitation of foot loading. Limb loading notably inhibited the H-reflex during both static condition and active or passive stepping. Thus, load-related afferent inputs play an essentially role in phase-dependence H-reflex modulation. The excitability of alpha-motoneurons in the most degree is influenced by afferent inflow from foot receptors.

[Locomotion induced by epidural stimulation in decerebrate cat after spinal cord injury].

The effect of partial and complete spinal cord injury (Th7-Th8) on locomotor activity evoked by epidural electrical stimulation (L5 segment, stimulation frequency 5 Hz, current strength 80-100 microA) in decerebrate cats has been investigated. It was established that the cutting of dorsal columns did not influence substantially the locomotion. The destruction of the ventral spinal quadrant resulted in the deterioration and instability of the locomotor rhythm. The injury of lateral or medial descending motor systems led to a redistribution of the tone in antagonist muscles. It was found that locomotion can be evoked by epidural stimulation within 20 h after the complete transaction of the spinal cord. The restoration of polysynaptic components in EMG responses correlated with the restoration of the stepping function. The data obtained confirm that the initiation of locomotion under epidural stimulation is caused by direct action on intraspinal systems responsible for locomotion regulation. In the case of intact or partially injured spinal cord, this effect is under the influence of supraspinal motor systems correcting and stabilizing the evoked locomotor pattern.

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.

Respiratory responses to voluntary and reflexly-induced stepping movements in normal subjects and spinal patients.

In the present study, the mechanisms of interaction between the breathing and stepping movements were investigated. The investigations were carried out in 8 normal subjects and 4 individuals with complete spinal cord lesion. Additionally, experimental studies were performed in 7 decerebrate and 4 spinal cats. Involuntary reflex stepping movements in the air were induced by vibrators attached above a tendon of m. rectus femoris and m. biceps femoris. In the spinal patients, epidural stimulation was carried out with electrodes located in the posterior epidural space at the vertebral level Th11. It was found that voluntary-induced stepping, which are accompanied by visceral reactions, were mediated by the central mechanisms. Changes in breathing pattern in response to vibration-induced involuntary stepping movements point up to the peripheral component being predominant in such interactions. In the spinal patients under epidural spinal cord stimulation delivered below the site of injury, the reaction in the cardio-respiratory system was abolished. Vibrations to the leg muscles also did not evoke respiratory responses. However, in the condition of forced breathing such vibrations evoked the rhythmic bursting EMG activity in m. rectus femoris, which was in harmony with the breathing rhythm. The results confirmed the presence of an interaction between breathing and stepping generators. This interaction is underlain both by central and peripheral components.