And yet it moves: Recovery of volitional control after spinal cord injury

Preclinical and clinical neurophysiological and neurorehabilitation research has generated rather surprising levels of recovery of volitional sensory-motor function in persons with chronic motor paralysis following a spinal cord injury. The key factor in this recovery is largely activity-dependent plasticity of spinal and supraspinal networks. This key factor can be triggered by neuromodulation of these networks with electrical and pharmacological interventions. This review addresses some of the systems-level physiological mechanisms that might explain the effects of electrical modulation and how repetitive training facilitates the recovery of volitional motor control. In particular, we substantiate the hypotheses that: (1) in the majority of spinal lesions, a critical number and type of neurons in the region of the injury survive, but cannot conduct action potentials, and thus are electrically non-responsive; (2) these neuronal networks within the lesioned area can be neuromodulated to a transformed state of electrical competency; (3) these two factors enable the potential for extensive activity-dependent reorganization of neuronal networks in the spinal cord and brain, and (4) propriospinal networks play a critical role in driving this activity-dependent reorganization after injury. Real-time proprioceptive input to spinal networks provides the template for reorganization of spinal networks that play a leading role in the level of coordination of motor pools required to perform a given functional task. Repetitive exposure of multi-segmental sensory-motor networks to the dynamics of task-specific sensory input as occurs with repetitive training can functionally reshape spinal and supraspinal connectivity thus re-enabling one to perform complex motor tasks, even years post injury

Rostral lumbar segments are the key controllers of hindlimb locomotor rhythmicity in the adult spinal rat

The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influence in rhythm initiation and generation. However, whether L2 will initiate hindlimb locomotion in the absence of S1 segments, and whether S1 segments can facilitate locomotion in the absence of L2 segments remain unknown. Herein, adult rats received complete spinal cord transections at T8 and then at either L2 or S1. Rats with spinal cord transections at T8 and S1 remained capable of generating coordinated hindlimb locomotion when receiving epidural stimulation at L2 and when ensembles of locomotor related loadbearing input were present. In contrast, minimal locomotion was observed when S1 stimulation was delivered after spinal cord transections at T8 and L2. Results were similar when the nonspecific serotonergic agonists were administered. These results demonstrate in adult rats that rostral lumbar segments are essential for the regulation of hindlimb locomotor rhythmicity. In addition, the more caudal spinal networks alone cannot control locomotion in the absence of the rostral segments around L2 even when loadbearing rhythmic proprioceptive afferent input is imposed.NEW & NOTEWORTHY The exact location of the spinal neuronal locomotor-related networks in adult mammals remains unknown. The present data demonstrate that when the rostral lumbar spinal segments (~L2) are completely eliminated in thoracic spinal adult rats, hindlimb stepping is not possible with neurochemical modulation of the lumbosacral cord. In contrast, eliminating the sacral cord retains stepping ability. These observations highlight the importance of rostral lumbar segments in generating effective mammalian locomotion

An Autonomic Neuroprosthesis: Noninvasive Electrical Spinal Cord Stimulation Restores Autonomic Cardiovascular Function in Individuals with Spinal Cord Injury

© Aaron A. Phillips et al. 2018. Despite autonomic dysfunction after spinal cord injury (SCI) being the major cause of death and a top health priority, the clinical management options for these conditions are limited to drugs with delayed onset and nonpharmacological interventions with equivocal effectiveness. We tested the capacity of electrical stimulation, applied transcutaneously over the spinal cord, to manage autonomic dysfunction in the form of orthostatic hypotension after SCI. We assessed beat-by-beat blood pressure (BP), stroke volume, and cardiac contractility (dP/dt; Finometer), as well as cerebral blood flow (transcranial Doppler) in 5 individuals with motor-complete SCI (4 cervical, 1 thoracic) during an orthostatic challenge with and without transcutaneous electrical stimulation applied at the TVII level. During the orthostatic challenge, all individuals experienced hypotension characterized by a 37 ± 4 mm Hg decrease in systolic BP, a 52 ± 10% reduction in cardiac contractility, and a 23 ± 6% reduction in cerebral blood flow (all p < 0.05), along with severe self-reported symptoms. Electrical stimulation completely normalized BP, cardiac contractility, cerebral blood flow, and abrogated all symptoms. Noninvasive transcutaneous electrical spinal cord stimulation may be a viable therapy for restoring autonomic cardiovascular control after SCI

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia.

An increasing number of studies supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes functional recovery in humans with spinal cord injury (SCI). However, the neural mechanisms contributing to these effects remain poorly understood. Here we examined motor-evoked potentials in arm muscles elicited by cortical and subcortical stimulation of corticospinal axons before and after 20 min of TESS (30 Hz pulses with a 5 kHz carrier frequency) and sham-TESS applied between C5 and C6 spinous processes in males and females with and without chronic incomplete cervical SCI. The amplitude of subcortical, but not cortical, motor-evoked potentials increased in proximal and distal arm muscles for 75 min after TESS, but not sham-TESS, in control subjects and SCI participants, suggesting a subcortical origin for these effects. Intracortical inhibition, elicited by paired stimuli, increased after TESS in both groups. When TESS was applied without the 5 kHz carrier frequency both subcortical and cortical motor-evoked potentials were facilitated without changing intracortical inhibition, suggesting that the 5 kHz carrier frequency contributed to the cortical inhibitory effects. Hand and arm function improved largely when TESS was used with, compared with without, the 5 kHz carrier frequency. These novel observations demonstrate that TESS influences cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. We hypothesized that these parallel effects contribute to further the recovery of limb function following SCI.SIGNIFICANCE STATEMENT Accumulating evidence supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes recovery of function in humans with spinal cord injury (SCI). Here, we show that a single session of TESS over the cervical spinal cord in individuals with incomplete chronic cervical SCI influenced in parallel the excitability cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. Importantly, these parallel physiological effects had an impact on the magnitude of improvements in voluntary motor output

Engaging cervical spinal circuitry with non-invasive spinal stimulation and buspirone to restore hand function in chronic motor complete patients

© 2018, The Author(s). The combined effects of cervical electrical stimulation alone or in combination with the monoaminergic agonist buspirone on upper limb motor function were determined in six subjects with motor complete (AIS B) injury at C5 or above and more than one year from time of injury. Voluntary upper limb function was evaluated through measures of controlled hand contraction, handgrip force production, dexterity measures, and validated clinical assessment batteries. Repeated measure analysis of variance was used to evaluate functional metrics, EMG amplitude, and changes in mean grip strength. In aggregate, mean hand strength increased by greater than 300% with transcutaneous electrical stimulation and buspirone while a corresponding clinically significant improvement was observed in upper extremity motor scores and the action research arm test. Some functional improvements persisted for an extended period after the study interventions were discontinued. We demonstrate that, with these novel interventions, cervical spinal circuitry can be neuromodulated to improve volitional control of hand function in tetraplegic subjects. The potential impact of these findings on individuals with upper limb paralysis could be dramatic functionally, psychologically, and economically

The Generalized Star Product and the Factorization of Scattering Matrices on Graphs

In this article we continue our analysis of Schr\"odinger operators on arbitrary graphs given as certain Laplace operators. In the present paper we give the proof of the composition rule for the scattering matrices. This composition rule gives the scattering matrix of a graph as a generalized star product of the scattering matrices corresponding to its subgraphs. We perform a detailed analysis of the generalized star product for arbitrary unitary matrices. The relation to the theory of transfer matrices is also discussed

О новой процедуре создания арбитражного учреждения

УДК 342.951+347.999This informational introductory article is devoted to the peculiarities of the procedure of creation of the arbitration institution according to the new 2015 Federal Law "On arbitration (arbitration proceedings)". The aim of the article is the identification of the new law preconditions to the emergence of administrative barriers in the establishment of arbitral institutions. The study is based on methods of formal law, analysis and synthesis, the sociological method of survey is also used. The results and scope of the results. The article notes the objective difficulties in the establishment of arbitration institutions as well as provides a critical analysis of the innovations in 2015 Federal Law "On arbitration (arbitration proceedings) in the Russian Federation". The procedure for creating the arbitration courts became more bureaucratic and it is focused on filtering such institutions by tightening the requirements. The procedure for creating the arbitration courts can be described as permissive and multi-stage. The second noticeable trend in the 2015 Federal Law is broad sphere of control over arbitration courts and substitution of their competence by a competent court. According to the results of a survey of representatives of the business community authors identify the legislative background of administrative barriers on a way of establishment of arbitration courts. The results of the study can be used in the improvement of legislative procedures for the estab-lishment of arbitration courts. Conclusions. New Law actually creates a "quasi-judicial" bodies, that have highest level of bureaucratization, so arbitration courts lose their main characteristics: contractual and dispositive principles. Novels of Law, aimed at stricter administration and control, are obvious, however, a new quality for arbitration as the most popular form of alternative dispute resolution is still not created.УДК 342.951+347.999Вступительная статья информационного характера посвящена особенностям процедуры создания арбитражного учреждения согласно новому Федеральному закону от 29 декабря 2015 г. № 382-ФЗ «Об арбитраже (третейском разбирательстве) в Российской Федерации». Отмечаются трудности объективного характера при создании арбитражных учреждений, проводится критический анализ нововведений закона о создании третейских судов

Проблемные аспекты предоставления субсидий субъектам предпринимательской деятельности: российский опыт

The subject of the paper is Russian the legal framework and law enforcement practice con-cerning granting subsidies to business entities.The purpose of the paper is to identify the legal problems of state support for small and medium – sized businesses by granting subsidies.The methodology of paper includes the formal logical interpretation of Russian legislation, systematization of the court practice concerning application of art. 15.15.5 (pt. 2) Code of Administrative Offences of the Russian Federation and other regulations.The main results and scope of their application. The legal basis of providing subsidies is characterized. The business support programs in Russia are analyzed. The author's ap-proach to the distinction between the concepts of "terms of granting subsidies”, “terms established when granting subsidies" and the "terms of using subsidies" is substantiated. The valid and invalid conditions for the granting of subsidies as well as the reasons for their return are proven. The results of research may be used as the basis of correction of Russian and foreign legislation concerning granting subsidies to business entities as well as step in future legal research in this sphere.Conclusions. Public authorities and local governments do not take into account differences between the terms "conditions for granting subsidies" and "conditions for the use of subsi-dies", unreasonably apply civil law norms to the rules for granting subsidies. Regional au-thorities do not effectively use the legal opportunities provided to them by the Federal leg-islator, as well as often allow the abuse of power.Выявляются правовые проблемы государственной поддержки малого и среднего биз-неса в форме предоставления субсидий. Охарактеризована правовая основа предо-ставления субсидий. Проведен анализ программ поддержки предпринимательства. На основе систематизации судебной практики применения ч. 2 ст. 15.15.5 КоАП РФ и иных норм предложен авторский подход к разграничению понятий «условия предо-ставления субсидий», «условия, установленные при предоставлении субсидий» и «условия использования субсидий», а также обоснованы допустимые и недопусти-мые условия предоставления субсидий, основания для их возврата