Novel method for activation of the locomotor circuitry in human

We examine the possibility for activation of the involuntary locomotion of the lower limbs by spinal electromagnetic stimulation (ES). The subject laid on the left side. The legs are supported in a gravity-neutral position by special mounting that to provide horizontal rotation in the hip, knee and ankle. ES (3 Hz and 1.56 Tesla) at the T11,-T12 vertebrae induced involuntary locomotor-like movements in the legs. The latency from the initiation of ES to the first EMG burst compoused 0.68 +/- 1.0 s and it shortened at increasing of the frequency ES from 3 Hz to 20 Hz. Thus, the spinal ES can unduce the activation of the locomotor movements in human.     

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.     

Are interlimb interactions disturbed in patients with Parkinson’s disease? A study under unloading conditions

During natural human locomotion, neural connections are activated that are typical of regulation of the quadrupedal walking. The interaction between the neural networks generating rhythmic movements of the upper and lower limbs depends on tonic state of each of these networks regulated by motor signals from the brain. Distortion of these signals in patients with Parkinson’s disease (PD) may lead to disruption of the interlimb interactions. We examined the effect of movements of the limbs of one girdle on the parameters of the motor activity of another limb girdle at their joint cyclic movements under the conditions of arm and leg unloading in 17 patients with PD and 16 healthy subjects. We have shown that, in patients, the effect of voluntary and passive movements of arms, as well as the active movement of the distal parts of arms, on the voluntary movement of legs is weak, while in healthy subjects, the effect of arm movements on the parameters of voluntary stepping is significant. The effect of arm movements on the activation of the involuntary stepping by vibrational stimulation of-legs in patients was absent, while in healthy subjects, the motor activity of arms increased the possibility of involuntary rhythmic movements activation. Differences in the effect of leg movements on the rhythmic movements of arms were found in both patients and healthy subjects. The interlimb interaction appeared after drug administration. However, the effect of the drug was not sufficient for the recovery of normal state of the neural networks in patients. In PD patients, neural networks generating stepping rhythm have an increased tonic activity, which prevents the activation and appearance of involuntary rhythmic movements facilitating the effects of arms on legs.     

Significance of peripheral feedback in stepping movement generation under epideral spinal cord stimulation

In acute experiments on decerebrated and spinalized cats, the role of peripheral afferent input from hindlimbs in stepping patterns formation under epidural spinal cord stimulation (ESCS), was investigated. The hindlimb muscles' electromyographic activity and kinematic parameters of evoked stepping were analyzed. It has been shown that epidural stimulation (20-100 microA, 5 Hz) of L4-L5 spine segments induced coordinated stepping on the treadmill belt. In conditions of weight-bearing support (stopped treadmill, hindlimbs lifted above the treadmill), the stepping rhythmic was unstable, stepping cycle period and its internal structure having changed as well. With increased speed of locomotion the stepping frequency increased due to the duration of the support phase decreasing. Forward stepping could be reversed to backward stepping by changing the direction of the treadmill belt movement. In 2-4 hours after complete spinal transection (T8-T9), the epidural stimulation elicited stepping movements on a moving treadmill only. It was found that the influence of peripheral feedback on initiation of the stepping after spinalization increased. Peripheral feedback seems to play a major role in determining the fundamental features of motor output during the ESCS.     

Noninvasive method to control the human spinal locomotor systems

The mechanism of interactions between receptor activation in the musculoskeletal system and stimulation of the spinal cord in the regulation of locomotor behavior was studied in healthy subjects. Afferent stimulation was tested for effect on the patterns of stepping movements induced by percutaneous stimulation of the spinal cord. A combination of percutaneous spinal cord stimulation and vibratory stimulation was shown to increase the amplitude of leg movements. It was demonstrated that vibratory stimulation of limb muscles at a frequency of less than 30 Hz can be used to control involuntary movements elicited by noninvasive stimulation of the spinal cord.     

Activation of interlimb interactions increases the motor output in legs of healthy subjects: Study under the conditions of arm and leg unloading

The effect of arm movements and movements of individual arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration-triggered stepping-like leg movements was studied under the conditions of horizontal support of the upper and lower limbs. The horizontal support of arms provided a significant increase in the rate of activation of locomotor automatism by noninvasive impact on tonic sensory inputs. The addition of active arm movements during involuntary stepping-like leg movements led to an increase in the EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. The movement of the shoulder joints led to an increase in the 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 knee and hip joints. At the same time, the movement of forearms and wrists had a similar facilitating effect on the physiological and kinematic characteristics of rhythmic stepping-like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of subthreshold vibration of leg muscles, voluntary arm movements led to activation of involuntary rhythmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhythmic stepping than during involuntary leg movements. Thus, the simultaneous movements of the 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.     

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?C40 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.     

Response of external inspiration to the movements induced by transcutaneous spinal cord stimulation

The dynamic of the parameters of lung ventilation and gas exchange have been studied in 10 young male subjects during involuntary stepping movements induced by transcutaneous spinal cord electrical stimulation applied in the projection of T ₁₁–T ₁₂ vertebrae and during voluntary stepping movements. It has been found that the transcutaneous spinal cord stimulation inducing stepping movements leads to an increase in breathing frequency and a reduction in tidal volume. These effects may be mediated by some neurogenic factors associated with muscular activity during stepping movements, the activation of abdominal expiratory muscles, and the interaction between the stepping pattern and breathing generators.     

Effects of circum-oesophageal lesion on the behaviour of the stick insect Carausius morosus

The co-ordination of the walking behaviour of decerebrate stick insects is examined and compared with normal behaviour. The walks are fully coordinated but undergo subtle changes in timing, have a longer average step period and show momentary pauses of 50 ms during the time course of protraction movements. In addition a new intersegmental reflex has been discovered. This tactile reflex is used to avoid errors in co-ordination that would be produced by posterior legs stepping onto the tarsi of the legs in front. The reflex has a latency of 100 ms and is easily observed in lesioned animals but is also active, although seldom seen, in slowly walking intact animals.     

Features of stepping pattern formation in decerebrated cats under epidural spinal cord stimulation

The mechanisms of stepping pattern formation initiated by epidural spinal cord stimulation in decerebrated cats, were investigated. It is shown that the ability to produce the stepping pattern involve the L3-L5 segments. In flexor muscle, the formation of stepping pattern under optimal stimulation frequency (5-10 Hz) of these segments is provided by polysynaptic activity with the latency 80-110 ms. In extensor muscle, this process is realized through interaction of monosynaptic reflex and polysynaptic activity. The stepping pattern under epidural stimulation is determined by spinal structures with modulation influence of the peripheral feedback.     

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.     

Mechanisms of stepping rhythm formation in decerebrated and chronic spinal cats under epidural stimulation

A study was made of the stepping pattern formation in decerebrated and in chronic spinal cats during epidural stimulation (ES). The hindlimb stepping performance depended on the parameters of ES and afferent input. At non-optimal ES parameters, no stepping was induced, only muscle reflexes followed the stimulation rhythm. Optimized ES (3–5 Hz, 50–100 μA for decerebrated and 20–30 Hz, 150–250 μA for spinal cats) evoked coordinated stepping movements at a natural rate (0.8–1 Hz) accompanied by electromyographic burst activity of the corresponding muscles. In decerebrated cats, the bursts are formed owing to modulation of early responses and the late polysynaptic activity. In chronic spinal cats, this process is mainly due to amplitude modulation of the early responses. Formation of the stepping pattern in decerebrated cats involves spinal interneurons responsible for the polysynaptic activity, which allows its correction based on processing the afferent signals. Activation of this system in chronic spinal cats can be realized by afferent stimulation alone, without ES.     

Mechanism of the Fast Neurogenic Component of the Ventilatory Response to the Initiation of Locomotor Activity

Experimental and clinical material allowed a quantitative assessment of the contribution of the central (cortical) and reflex (proprioceptive) components to the origin of the initial phase of exercise-associated hyperpnea and modulation of this ventilatory response depending on the excitability of central and peripheral chemoreceptors. It was established that, in healthy subjects, the pattern of involuntary stepping movements induced by vibration ("stepping in the air") significantly changes its characteristics during hypercapnic stimulation of the respiratory center. In spinal patients, voluntarily increased ventilation of the lungs induces rhythmic EMG activity in the musculus rectus femoris according to the respiratory rhythm. This phenomenon was explained by the stretch reflexes from the expiratory abdominal muscles, impulses from which might affect the lumbar motoneurons, bypassing the site of lesion. These data clearly demonstrate the real mechanisms of interactions between the regulations of the locomotor and autonomic functions of the body and provide a theoretical basis for the principal possibility of controlling locomotor activity by regulating respiratory movements, which can be used in clinical practice for the rehabilitation of spinal patients.     

Electromyographic characterization of walking behavior initiated spontaneously in crayfish

Crayfish initiate walking behavior not only reflexively in response to external stimuli but also spontaneously in the absence of any specific stimulus. In order to analyze the initiation mechanism underlying these different types of walking, we made simultaneous electromyographic (EMG) recordings from thoracic legs when animals initiated walking, either reflexively or spontaneously, and video recorded their movements synchronously with the EMG recording. Two different stimuli, mechanical and chemical, were used to reflexively induce walking. A non-rhythmic, sustained activation of leg muscles was found to precede the behavioral initiation of either type of walking. The duration of this non-rhythmic muscle activation was significantly longer in the spontaneously initiated walking than in the mechanical stimulus-evoked walking, although no difference was observed between the spontaneous and chemical stimulus-evoked walking. EMG recordings from all eight legs revealed that their non-rhythmic muscle activation occurred almost simultaneously prior to initiation of rhythmical stepping movements. When an animal was suspended without a leg substratum, the timing of muscle activation was more variable among the legs than in the free condition on the substratum. When the circumesophageal commissures were both severed to eliminate signals descending from the brain to the thoracic ganglia, the bilaterally coordinated rhythmic burst activity was not observed in the walking legs. These findings suggest that the spontaneous initiation of walking behavior requires sensory feedback signals from leg proprioceptors, subserved by a different descending activation mechanism from that for stimulus-driven initiation of walking.     

Effects of transcutaneous electrical spinal cord stimulation on stepping patterns during walking

Effects of transcutaneous electrical spinal cord stimulation (tESCS) on the parameters of stepping movements in healthy subjects were investigated during two kinds of activity: walking on a moving treadmill belt (active treadmill) as well as pushing the treadmill belt by effort of the legs (passive treadmill). It was found that the total interference electromyogram (EMG) activity during stepping performance on a passive treadmill was 1.5–2 times higher than during stepping on an active treadmill. In addition, the amplitude of angular displacement of the hip joint and ankle was 2.5 times and 1.7 times higher, respectively, during passive vs. active treadmill, while the duration of stepping cycle decreased by 19%. Although the muscles were exposed to different load and the parameters of motion on the active and passive treadmill were different, tESCS caused an increase in the total EMG activity in 96% of cases both on the active and on the passive treadmill. In both cases, the stepping cycle period decreased by 4–43% in all subjects. These results suggest that tESCS can affect voluntary stepping patterns under conditions of different afferent control.     

Rotational locomotion by the cockroach Blattella germanica

Locomotion on complex substrata can be expressed in a plane by two geometric components of body movement: linear locomotion and rotational locomotion. This study examined pure rotation by analysing the geometry of leg movements and stepping patterns during the courtship turns of male Blattella germanica. Strict rotation or translation by an insect requires that each side of the body cover equal distance with respect to the substrate. There are three mechanisms by which the legs can maintain this equality: frequency of stepping, magnitude of the leg arcs relative to the body and the degree to which legs flex and extend during locomotion. During the courtship behaviour of Blattella germanica selected males executed turns involving body rotation along with leg movements in which the legs on the outside of the turn swung through greater average arcs than those on the inside of the turn. This difference should have resulted in a translation component. However, legs on the inside of the turn compensated by flexion and extension movements which were greater than those of opposing legs. The net effect was that both sides of the body covered equal average ground. These cockroaches used a wide variety of stepping combinations to effect rotation. The frequency of these combinations was compared to an expected frequency distribution of stepping combinations and further to an expected frequency of these stepping combinations used for straight walking. These comparisons demonstrated a similarity between interleg coordination during straight walking and that during turning in place.     

Activation of walking by electrical stimulation in humans under the conditions of muscle unloading and its variations under the effect of afferent influences

The possibility of initiating an involuntary walking rhythm in a suspended human leg by electrical stimulation was studied. The subjects lay on the side with one leg suspended in an exoskeleton allowing horizontal rotation in three joints: the hip, knee, and ankle ones. To evoke involuntary walking of the suspended leg, two methods were used: continuous vibration of the quadriceps muscle of the hip and electrical stimulation of the cutaneous nerves innervating the foot of the immobile leg. The hip and ankle were involved in the involuntary movements, with reciprocal bursts of electromyographic activity being also observed in the antagonistic muscles of the hip. The application of an external load (4 N or 8 N) to the foot caused a perceptible intensification of its movements. An additional weight (0.5 kg) or a rubber band wrapped around the foot caused no substantial change in the pattern of stimulated walking. Electrical stimulation is an effective means of activating walking movements, and their characteristics confirm the assumption that the walking rhythm is of central origin. Additional afferentation from the sole’s receptors plays an important role in the modulation of the induced movements and the modification of the general walking pattern under the conditions of muscle unloading.     

Brainstem pathways of the initiation of locomotion

Conclusion This overview of the brainstem pathways of the initiation of locomotion can be summarized as follows. There are locomotor regions (hypothalamic and mesencephalic) whose stimulation leads to the appearance of rhythmic stepping movements. These regions are nonuniform in composition: transient fibers as well as cells are found. The locomotor effects of electrical stimulation of these regions can largely be explained on the basis of the presence of efferent projections of the neurons to the medial reticular formation, as well as the activation of the transient fibers of other brain systems. The ventromedial parts of the reticular formation of the medulla oblongata, including areas of the macrocellular and (to a lesser extent) gigantocellular nuclei, form the final element in the suprasegmental system of locomotion initiation. The inconclusive data of different scientists who have used chemical microinjections into the locomotor regions make it impossible at present to specify precisely the neurochemical mechanisms underlying the initiation of locomotion. NMDA has been found to play an important role. The activation of the reticular formation during the triggering of stepping movements can take place either from the locomotor regions or by means of signals coming from the collaterals of the ascending sensory tracts. The wide spectrum of possible pathways of the initiation of locomotion apparently affords the organism a choice of ways by which to realize this process and is an important factor in its adaptation to its environment.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 4, pp. 488–505, July–August, 1991.     

Role of afferent activity in the generation of stepping movements

Efferent fibers of the hind limbs were divided and electrical activity of a filament from the ventral root of S1 was recorded in experiments on mesencephalic cats capable of locomotion in response to stimulation of the "locomotor region" of the midbrain. In response to weak stimulation of the locomotor region, when the forelimbs were not performing stepping movements, regular waves of activity appeared in the filament with a period close to the duration of the step during walking (0.5–1.0 sec). This periodic process was largely dependent on the tonic afferent inflow: various extero- and interoceptive stimuli applied to the hind limb could change the period of generation or abolish it. Active stepping movements of the forelimbs as well as passive movements of the hind limbs led to synchronization of activity in the filament with these movements. After division of the afferent fibers to the hind limbs the animals performed one or two steps in response to stimulation of the dorsal root of S1 by a short series of pulses. They could also perform independent stepping movements of the hind limb if 15–30% of the fibers in the dorsal root of L7 remained intact.M. V. Lomonosov Moscow State University. Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 401–409, 1972.     

Dynamics of hormone release from the perfused canine thyroid during cyclic AMP infusion.

In order to try to characterize the sequence of processes leading to hormone secretion from the stimulated thyroid, the effect of cyclic 3'5' adenosine monophosphate (cAMP) and related compounds were examined in 15 two-sided perfusions of canine thyroids isolated in situ. T4 and T3 concentrations in the effluent were measured radioimmunologically. cAMP 5 mM and TSH 100 muU per ml induced the same pattern of hormone release from the thyroid. After a latency period of 15--25 minutes a steep increase occurred in both T4 and T3 release. During the initial part of the stimulation the rise in T4 relase was somewhat slower than that of T3 release. The prolonged latency period before response earlier recorded in the same preparation during infusions of low concentrations of TSH was not observed during infusions of decreasing concentrations of cAMP (1, 0.8, 0.5 and 0.2 mM) or theophylline (5 and 1 mM). Either there was no response or the latency period was of the same length as that observed after a strong stimulus. These findings suggest that the latency period can be divided in two parts: () a variable, dose dependent satency period confined to the early part of the process sequence leading to secretion--i.e. before cAMP exerts its effect, and 2) an obligatory latency period related to the processes taking place after the formation of pseudopods. The duration of these late processes seems to be independent of the degree of stimulation.