Regulation of Human Respiration by Electrical Stimulation.

The review addresses modern methods of electrical stimulation used to regulate the function of external respiration in humans. The methods include abdominal functional stimulation of respiratory muscles, diaphragmatic stimulation, phrenic nerve stimulation, epidural and transcutaneous spinal cord stimulation. The physiological rationale of their application is described along with the examples of their use in clinical practice, including stimulation parameters and electrode placement diagrams for each of the methods. We analyze the effectiveness of each of the methods in patients with respiratory muscle paresis and the features of their use depending on the level of spinal cord injury. Special attention is paid to the method of epidural spinal cord stimulation because this technique is widely used in electrophysiological studies on animal models, providing deeper insight into the spinal levels of the functional control of external respiration. The review substantiates the great potential of using the method of transcutaneous electrical spinal cord stimulation both in fundamental studies of external respiration and in clinical practice.

A New Technology for Recovery of Locomotion in Patients after a Stroke.

Neural networks in the spinal cord can generate the walking pattern and control posture in the absence of supraspinal influences. A technology using transcutaneous electrical spinal cord stimulation (tSCS) was created. During walking, tSCS activated spinal locomotor networks, as well as leg flexor/extensor motor pools in the swing/stance phases, respectively. It was assumed that the use of this technology in subjects with locomotion disorders would improve walking. Patients with hemiparesis were studied 3-11 months after stroke, the duration of the course was 2 weeks. Patients of the main and control groups received standard therapy and rehabilitation using the technology; in the control group, sham tSCS was used. After the course, minimal clinically important differences in walking parameters were achieved in the main group, in contrast to the control group. The developed technology is an effective means of restoring walking in patients with hemiparesis.

[Noninvasive spinal cord electrical stimulation in the complex rehabilitation of patients with spinal cord injury]. / Neinvazivnaia élektricheskaia stimuliatsiia spinnogo mozga v kompleksnoi reabilitatsii bol'nykh so spinnomozgovoi travmoi.

BACKGROUND: Spinal cord injury causes significant impairments of both motor and pelvic organ functions. Latest studies have shown impressive potentials for using transcutaneous spinal cord electrical stimulation (TcSCES) in the late period of injury to restore motor functions. All results were obtained in a limited number of patients in the specific conditions of a physiological experiment. It remains unclear how effective a TcSCES cycle is in restoring motor activity in patients after spinal cord injury in real clinical conditions. AIM: The main objective of this investigation was to study the effectiveness of TcSCES in combination with the standard rehabilitation of patients after a spinal cord injury. An additional objective was to evaluate the effect of TcSCES to excretory functions in patients with spinal cord injury. SUBJECTS AND METHODS: The studies were conducted at Saint Petersburg City Hospital Forty, which included 15 patients with thoracic spinal injury at 2.4±2.06 years after injury; the severity of the latter was American Spinal Injury Association (ASIA) Grades B and C. All the patients underwent a 2-week standard cycle of rehabilitation treatment; of them 7 patients (a study group) received additionally TcSCES. Standard scales were used to assess neurological status and muscle strength and sensitivity. The patients filled out a urinary diary; residual urine volume was monitored using bladder catheterization or ultrasound. RESULTS: An increase in muscle strength was recorded in 6 patients of the study group and in 1 patient of the control one. The end of the treatment cycle was marked by a 1-score spasticity increase in 1 patient of the study group and in 2 patients in the control one. In the study group, the level of anesthesia decreased per segment in 1 patient; an improvement in deep and proprioceptive sensitivity was recorded in 2 patients; no change in sensitivity was observed in the control group. In the study group, 2 patients showed a reduction in the severity of injury from ASIA Grade B to ASIA Grade C. In three patients of the study group, the residual urine volume decreased and control and a sensation of urgency to urinate appeared; in the control group, these parameters remained unchanged after the treatment cycle. DISCUSSION: The main result of the study is evidence for the efficiency of using TcSCES in the complex therapy of motor neurorehabilitation. The performed cycle of TcSCES in patients was noted to result in better motor and excretory functions. CONCLUSION: The use of a short-term TcSCES cycle in the motor rehabilitation program for patients with spinal cord injury contributes to recovery of severe motor disorders and is accompanied by an improvement in urinary functions.

Mechanisms of Blood Flow Regulation in the Skin during Stimulation of the Spinal Cord in Humans.

Changes in the blood flow in the shin skin were observed by laser Doppler flowmetry after transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz in 12 healthy subjects. It was found that TSCS in the area of the T11 and L1 vertebrae led to a significant increase in skin blood flow. The microcirculation rate increased by more than 85% relative to the baseline at a stimulus intensity of 90% of the motor threshold. Cutaneous blood flow activization by TSCS is implemented mainly through the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important mediator that contributes to vasodilation and increase in cutaneous blood flow upon TSCS. NO is predominantly of endothelial origin.

Effects of spinal cord stimulation on motor functions in children with cerebral palsy.

Is it possible to regulate the functional properties of abnormally developed spinal neuronal locomotor networks using transcutaneous spinal cord stimulation? This question has been studied in twenty-eight participants (∼9 yrs) with spastic cerebral palsy, and mainly Gross Motor Function Classification System for Cerebral Palsy level III. The participants were randomly assigned to two groups. The experimental group received transcutaneous spinal cord stimulation at two spinal levels (over T11 and L1 spinous processes), combined with locomotor treadmill training, whereas the participants of the control group received locomotor treadmill training only. After spinal cord stimulation in the experimental group we found an incremental increase in knee torque whereas in the control group this effect was absent. The amplitude of hip motion increased in both groups. A decrease of co-activation of hip and muscles of the lower extremities was observed in the experimental group while in the control group co-activation decreased only in hip muscles. The results support the idea that locomotor function can be improved significantly with the combination of training and transcutaneous spinal cord stimulation than with training alone.

[The regulation of balance in the children presenting with severe cerebral palsy following the treatment with the use of the locomotor training in combination with the electrical stimulation of leg muscles and spinal cord]. / Regulyatsiya balansa u detei s tyazhelymi formami detskogo tserebral'nogo paralicha posle lokomotornykh trenirovok v kombinatsii s elektrostimulyatsiei myshts i spinnogo mozga.

One of the cerebral palsy (CP) symptoms is the impairment of the ability to maintain upright standing. The objective of the present study was to investigate the effect of the locomotor training combined with electrical transcutaneous spinal cord stimulation (TSCS) and functional electrical stimulation (FES) of the muscles to facilitate the restoration of the vertical posture function in the children presenting with cerebral palsy. PATIENTS AND METHODS: This article is designed to present the results of the study that included 19 patients at the age from 6 to 12 years. The severity of the CP clinical manifestations was estimated to be around 3 in accordance with The Gross Motor Function Classification System (GMFCS). All the patients underwent 15 half-hour daily sessions of robotic mechanotherapy with the use of a locomotor training device. In 8 patients from the main group, each locomotor training session was accompanied by the TSCS and FES procedures. The patients of the control group underwent the locomotor training alone. RESULTS: The dynamics of regaining the standing posture regulation was evaluated by stabilometry that has revealed a significant increase of postural stability in the children of the main group in comparison with those in the control group. It was apparent as a statistically significant (p<0.05) reduction of the length and the area of the center of pressure (COP) projection with open eyes (the 167 mm and 112 mm2 decrease of the median, respectively). In addition, the tendency toward the normalization of the COP projection in the sagittal plane was documented. CONCLUSION: The present study has demonstrated the normalization of the impaired balance control system in the children presenting with the severe form of cerebral palsy under the influence of the combined treatment with the use of transcutaneous spinal cord stimulation and functional electrical stimulation of legs muscles supplemented by the locomotor training.

Effect of Combination of Non-Invasive Spinal Cord Electrical Stimulation and Serotonin Receptor Activation in Patients with Chronic Spinal Cord Lesion.

We analyzed the efficiency of percutaneous electrical stimulation of the spinal cord and serotonin receptor activation in rehabilitation of paralyzed patients. Four-week course of spinal cord electrical stimulation combined with mechanotherapy produced positive shifts in the status of chronically paralyzed patients. Serotonin receptor activation potentiated the effect of spinal cord stimulation and can be regarded as an additional neurorehabilitation option.

[Non-Invasive Methods for the Control of Human Spinal Locomotory Systems].

We studied the interrelations between the activation of the receptors of musculoskeletal system and the spinal cord stimulation in the regulation of locomotor behavior in healthy subjects. We observed the effect of afferent stimulation on the patterns of stepping movements caused by percutaneous stimulation of spinal cord. It was found that the combination of percutaneous spinal cord stimulation and vibrostimulation increases the amplitude of leg movements. It was shown that the vibrostimulation of limb muscles at a frequency of less than 30 Hz may be used for comtrolling involuntary movements, caused by non-invasive stimulation of the spinal cord.

[Mehanisms of Influences of Electrical Spinal Cord Stimulation on Autonomic Functions.]

Recently transcutateous electrical spinal cord stimulation began to be used both for experimental studies of motor functions regulation and for rehabilitation of motor functions in patients with spinal cord injury. The spinal cord is a very important center of vital functions regulation and the spinal cord stimulation directed to the activation of spinal locomotor related networks will affect visceral systems as well. This circumstance is necessary to take into account when this new method will be used for rehabilitation as well as for the studies on healthy subjects. Here the review of publications related to effects of electrical spinal cord stimulation on peripheral and cerebral circulation, on the cardiovascular, respiratory, excretory, and digestive systems of mammals is presented.

[Evaluation of motor neuron excitability in lumbosacral spinal cord: Transcutaneous spinal cord stimulation as compared to H-reflex].

Multisegmental muscle responses (MMR) are reflexes in the leg muscles evoked by transcutaneous electrical spinal cord stimulation over the Th11­Th12 vertebrae. We have used MMR to evaluate the excitability of lumbosacral motor neurons in individuals suffering lower paraplegia. Ten individuals were tested using H-reflexes and MMR bilaterally before (n 0 = 20) and during 4-weeks course of rehabilitation (n=76). The H-reflex and MMR of m. gastrocnemius lateralis were obtained in: 15 and 13 cases out of 20, respectively. Both reflexes were recorded in 11 and were absent in 3 cases, matched up to 70% of recordings. In dynamic, the both methods were 100% reproducible and the responses' amplitude varied in similar directions in 67% of records. The data confirm the validity and reproducibility of the MMR for evaluation of the motor neurons excitability in lumbosacral cord. The H-reflex magnitude shows moderate correlation with MMR in m. gastrocnemius lateralis (r = 0.59, p < 0.001), and low correlation with MMR in mm. rectus femoris, biceps femoris, and tibialis anterior (r < 0.40, p < 0.001). These findings do not allow extrapolate the results from the H-reflex measurement on the state of lumbosacral cord. At the same time, measurements of the MMR allow estimate simultaneously the excitability of motor pools innervating several muscle groups. This makes advantageous to assess the functional state of the motor neurons in the lumbosacral spinal cord for clinical and experimental studies, including the spinal cord damage.

[Effects of locomotor training and functional electrical stimulation on postural function in children with severe cerebral palsy].

Cerebral palsy (CP) considerably impairs the ability to maintain upright stance. In the present study the effects of locomotor training and functional electrical stimulation (FES) on postural control have been determined in children (n = 27) aged 6­12 years with severe CP. The severity level of the CP clinical manifestations was determined as 3 according to the Gross Motor Function Classification System (GMFCS) classification. All patients participated in 15 half-hour sessions of mechanic therapy using robot-assisted passive stepping. In 12 out of 27 children, the locomotion therapy was accompanied with FES. Stabilometry and plantography tests were performed before and after the course of interventions. In addition, similar posturographics tests were performed in 23 healthy children same age. Postural control in children with CP was characterized by a forward shift of the center of pressure (COP) projection; higher values of the COP trajectory area and length, as weel as by mean amplitude of the COP oscillations, and the absence of COP response to the eyes closed condition. After treatment, the posturographic characteristics had a tendency to normalization in relation to the values obtained in neurologically intact children. The improvement was observed in 43% of children without FES and in 75% of children which used FES. Analysis of plantograms revealed normalization of footprints in children received FES. Thus, it was demonstrated that FES combined with locomotor training resulted in the improvement in vertical posture control in children with severe CP.

[Neurorehabilitation of Patients with Cerebral Palsy].

Cerebral palsy is one of the common diseases that cause significant motor impairments. This review deals with new methods of motor rehabilitation of children with cerebral palsy in terms of modern physiology, as well as with summarized and analyzed results of experimental studies on the effectiveness of these methods.

[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.

Effects of spinal cord electrical stimulation in patients with vertebrospinal pathology.

Until now, no scientific neurophysiologic methods of diagnostics and treatment of vertebrospinal pathologies were developed. Previous study showed that electrical stimulation of lumbar segments of the spinal cord in animals with complete spinal cord transection induced a well-coordinated weight-bearing locomotion. The present comparative study of motor activity triggered by electrical epidural stimulation of one or two segments of the spinal cord in spinal patients showed that stimulation of lumbar (L2-L4) or sacral (S2) segments facilitated generation of motor patterns of muscle activity. Combination of electrical stimulation with locomotor training resulted in the appearance of stepping patterns characteristic of normal walking and tonic activity of the muscles needed for body balance maintenance.

[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.

[Serotoninergic system morphofunctional aspects in control of postural and locomotion function].

Different mediator systems including serotoninergic one can influence animal's locomotor behavior. It has been shown that the spinal cord in the absence of supraspinal control is able to induce the locomotor activity in hindlimbs and afferent system can activate this mechanism. In behavioral studies on the rats with complete transection of the spinal cord it has been demonstrated that the pharmacological blocking of serotoninergic system results in depression of motor activity mediated by activation of support reactions. Histological studies did not reveal any effects of activation of support reactions on the safety of neurons as well as on the distribution of synaptic contacts within L2-L4 spinal segments. At the same time it has been shown that blockade of the serotoninergic system results in alterations of cells located in 1-3 laminae of dorsal horns, and in 7 Rexed's lamina as well as in redistribution of synaptic contacts in 1-4 Rexed laminae of the spinal cord dorsal horns.

[Analysis of locomotor activity in decerebrated cats during electromagnetic and epidural electrical spinal cord stimulation].

It was shown that the epidural and the electromagnetic tonic stimulation with frequency 5 Hz applied to the lumbal as well as to the cervical region of the spinal cord enabled stepping on a moving treadmill belt in decerebrated cats. It was found that there were differences in initiation of the stepping movements during epidural and electromagnetic stimulation depending on the region of spinal cord stimulation. Stimulation at frequency of 0.3 Hz induced single reflex responses in the anterior and posterior limbs. On the basis of analysis of the response structure it was concluded that the locomotor ability during epidural and electromagnetic stimulation depended on the degree of polysynaptic pathways activation. The hypothesis about stepping pattern generator activation through the dorsal roots during epidural stimulation and more direct activation of neuronal locomotor networks in the case of electromagnetic spinal cord stimulation is discussed.

Morphofunctional characteristics of the lumbar enlargement of the spinal cord in rats.

The topography of the lumbar enlargement of the spinal cord in rats was studied; an immunohistochemical method was used to determine the distribution of synaptophysin--a membrane protein of synaptic vesicles. Synaptophysin-immunoreactive structures were detected in the gray matter of all Rexed laminae, around most neurons and in the neuropil. Previously undescribed subpial synaptic contacts were detected immunohistochemically in the white matter and confirmed by electron microscopy. A non-myelinated component of the corticospinal tract, including axonal varicosities and synaptic contacts, was observed in the dorsal part of the white matter of the lumbar enlargement of the spinal cord.

[Morphofunctional characteristic of the rat distal spinal cord after its complete experimental section with subsequent treadbun training of the animal].

Motor activity of rats has been studied after complete experimental section of spinal cord at the lower thoracic level. A treadbun training performed one day after the operation has been shown to lead to the appearance of movement of hindlimbs and to restoration of function of support of the body weight. In our opinion, the key moment in initiation of locomotor movements is stimulation of foot. Morphoimmunohistochemical study (detection of nuclear protein of proliferation cells, synaptophysin, and glial fibrillary acid protein) of the lumbar enlargement has allowed revealing reorganization of motoneurons, interneurons, and afferent chain in the distal part of the sectioned spinal cord. In trained animals there are observed the normal structure of motoneurons and the appearance of aggregates of synaptophysin-immunoreactive structures lost after the operation.