Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury

ObjectiveThe importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans.MethodsUlnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants.ResultsPotentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones.ConclusionsDescending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation.SignificanceEvaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..     

Multi-joint movement of the cat hindlimb evoked by microstimulation of the lumbosacral spinal cord

Microstimulation of the lumbosacral spinal cord may be an effective tool for the restoration of locomotion after spinal cord injury. To examine this possibility, complex coordinated multi-joint hindlimb movements were evoked by electrical stimulation with sine waveform modulation using a single microelectrode positioned in the L5–S1 spinal cord. Four types of hindlimb movement (flexion, extension, abduction, and adduction) were identified, and their stimulation locations were mapped onto cross-sectional drawings of L5–S1 spinal cord following histological examination of electrode tracks in the cord. Hindlimb flexion was evoked without abduction/adduction at many locations in the dorsal part of the L5–S1 spinal cord, whereas extension was evoked with abduction/adduction in the ventral part of the cord. Bilateral reciprocal lifting of the hindlimb was evoked by implanting two microelectrodes (one on each side) in the spinal cord. This study indicates that functional hindlimb movements can be elicited by activating a small number of sites in lumbosacral spinal cord.     

Using EMG to deliver lumbar dynamic electrical stimulation to facilitate cortico-spinal excitability

BackgroundPotentiation of synaptic activity in spinal networks is reflected in the magnitude of modulation of motor responses evoked by spinal and cortical input. After spinal cord injury, motor evoked responses can be facilitated by pairing cortical and peripheral nerve stimuli.ObjectiveTo facilitate synaptic potentiation of cortico-spinal input with epidural electrical stimulation, we designed a novel neuromodulation method called dynamic stimulation (DS), using patterns derived from hind limb EMG signal during stepping.MethodsDS was applied dorsally to the lumbar enlargement through a high-density epidural array composed of independent platinum-based micro-electrodes.ResultsIn fully anesthetized intact adult rats, at the interface array/spinal cord, the temporal and spatial features of DS neuromodulation affected the entire lumbosacral network, particularly the most rostral and caudal segments covered by the array. DS induced a transient (at least 1 min) increase in spinal cord excitability and, compared to tonic stimulation, generated a more robust potentiation of the motor output evoked by single pulses applied to the spinal cord. When sub-threshold pulses were selectively applied to a cortical motor area, EMG responses from the contralateral leg were facilitated by the delivery of DS to the lumbosacral cord. Finally, based on motor-evoked responses, DS was linked to a greater amplitude of motor output shortly after a calibrated spinal cord contusion.ConclusionCompared to traditional tonic waveforms, DS amplifies both spinal and cortico-spinal input aimed at spinal networks, thus significantly increasing the potential and accelerating the rate of functional recovery after a severe spinal lesion.     

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.     

Influence of spinal cord injury on core regions of motor function

Functional electrical stimulation is an effective way to rebuild hindlimb motor function after spinal cord injury.However,no site map exists to serve as a reference for implanting stimulator electrodes.In this study,rat models of thoracic spinal nerve 9 contusion were established by a heavy-impact method and rat models of T6/8/9 spinal cord injury were established by a transection method.Intraspinal microstimulation was performed to record motion types,site coordinates,and threshold currents induced by stimulation.After transection(complete injury),the core region of hip flexion migrated from the T13 to T12 vertebral segment,and the core region of hip extension migrated from the L1 to T13 vertebral segment.Migration was affected by post-transection time,but not transection segment.Moreover,the longer the post-transection time,the longer the distance of migration.This study provides a reference for spinal electrode implantation after spinal cord injury.This study was approved by the Institutional Animal Care and Use Committee of Nantong University,China(approval No.20190225-008) on February 26,2019.     

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.     

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation

Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.     

Use of magnetic stimulation to elicit motor evoked potentials, somatosensory evoked potentials, and H-reflexes in non-sedated rodents

Assessment of locomotor function of rodents may be supplemented using electrophysiological tests which monitor the integrity of ascending and descending tracts as well as the focal circuitry of the spinal cord in non-sedated rodents. Magnetically induced SSEPs (M-SSEPs) were elicited in rats by activating the hindpaw using magnetic stimulation (MS). M-SSEP response latencies were slightly longer than those elicited by electrical stimulation. M-SSEPs were eliminated following selective dorsal column lacerations of the spinal cord, indicating that they were transmitted via this tract. Magnetically induced motor evoked potentials (M-MEPs) were elicited in mice following transcranial MS and recorded from the gastrocnemius muscles. M-MEPs performed on myelin deficient mice demonstrated longer onset latencies and smaller amplitudes than in wild-type mice. Magnetically induced H-reflexes (MH-reflexes) which assess local circuitry in the lumbosacral area of the spinal cord were performed in rats. This response disappeared following an L3 contusion spinal cord injury, however, kainic acid (KA) injection at L3, known to selectively destroy interneurons, caused a shorter latency and an increase in the amplitude of the MH-reflex. M-SSEPs and MH-reflexes in rats and M-MEPs in mice compliment locomotor evaluation in assessing the functional integrity of the spinal cord under normal and pathological conditions in the non-sedated animal.     

Neuromodulation of lower limb motor control in restorative neurology

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system.     

A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury

Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury.The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation.To activate lower-limb muscles precisely by epidural spinal cord stimulation,we proposed a high-density,flexible electrode array.We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord,which was established by a transection method.For evaluating the effect of stimulation,the evoked potentials were recorded from bilateral lowerlimb muscles,including the vastus lateralis,semitendinosus,tibialis anterior,and medial gastrocnemius.To determine the appropriate stimulation sites and parameters of the lower muscles,the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation.In the vastus lateralis and medial gastrocnemius,these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment,respectively.The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles.The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius.Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array.They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury.This study was approved by the Animal Research Committee of Southeast University,China(approval No.20190720001) on July 20,2019.     

Electrophysiological characteristics of lumbosacral evoked potentials in patients with established spinal cord injury

Surface electrodes positioned over the S1 and T12 vertebrae and referenced to T6 were used to record spinal potentials evoked by unilateral stimulation of the posterior tibial nerve at the knee. Data were collected on 24 patients who received spinal cord injuries 2 months to 31 years previously. The recording sites were below the level of spinal injury. The lumbosacral evoked potentials (LSEPs) were compared with the results of measurements obtained from 19 neurologically healthy subjects. Additional data were collected on each patient to characterize segmental reflex responses and preservation of sensory and motor functions associated with the L5 through S2 segments of the spinal cord. Assuming that the LSEP reflects the activity of spinal cord interneurons, the results demonstrate a degree of spinal cord dysfunction caudal to the area of injury in a substantial number of the patients with spinal cord injury which we studied.     

Artificial autonomic reflexes: using functional electrical stimulation to mimic bladder reflexes after injury or disease

Autonomic reflexes controlling bladder storage (continence) and emptying (micturition) involve spinal and supraspinal nerve pathways, with complex mechanisms coordinating smooth muscle activity of the lower urinary tract with voluntary muscle activity of the external urethral sphincter (EUS). These reflexes can be severely disrupted by various diseases and by neurotrauma, particularly spinal cord injury (SCI). Functional electrical stimulation (FES) refers to a group of techniques that involve application of low levels of electrical current to artificially induce or modify nerve activation or muscle contraction, in order to restore function, improve health or rectify physiological dysfunction. Various types of FES have been developed specifically for improving bladder function and while successful for many urological patients, still require substantial refinement for use after spinal cord injury. Improved knowledge of the neural circuitry and physiology of human bladder reflexes, and the mechanisms by which various types of FES alter spinal outflow, is urgently required. Following spinal cord injury, physical and chemical changes occur within peripheral, spinal and supraspinal components of bladder reflex circuitry. Better understanding of this plasticity may determine the most suitable methods of FES at particular times after injury, or may lead to new FES approaches that exploit this remodeling or perhaps even influence the plasticity. Advances in studies of the neuroanatomy, neurophysiology and plasticity of lumbosacral nerve circuits will provide many further opportunities to improve FES approaches, and will provide "artificial autonomic reflexes" that much more closely resemble the original, healthy neuronal regulatory mechanisms.     

电针刺激脊髓损伤患者穴位的脊髓磁共振功能成像激活区特征****☆

背景：研究发现脊髓功能激活区域和电生理等理论对应区域相一致,多数学者认为使用功能磁共振技术检测脊髓神经功能是可行的。 目的：检测电针刺激脊髓损伤患者的脊髓磁共振功能成像激活区特征,验证使用脊髓磁共振功能成像技术来客观评价针灸治疗脊髓损伤疗效的可行性。 方法：使用电针同时刺激3例脊髓损伤患者和5名健康志愿者的右手合谷穴和曲池穴,采用组块设计方法,使用SPM2软件得到患者和健康志愿者脊髓内真实的激活区,分析激活区在矢状位和横断位上的分布特征,并与健康志愿者的激活分布对比,找出患者的激活分布差异。 结果与结论：5名健康志愿者在脊柱C2、C5段均重复出现激活信号,在C6段4名出现激活;3例脊髓损伤患者在脊柱C2,C6段均出现均重复出现激活,其中1例患者与健康志愿者激活分布特征基本一致。可以观察到针灸刺激脊髓损伤患者的脊髓功能激活,因此可以根据功能激活区的分布及强度,在一定程度上客观评价针灸治疗脊髓损伤的疗效。 关键词：磁共振功能成像;脊髓损伤;针灸;穴位;SEEP;数字化图像与影像     

Training locomotor networks

For a complete adult spinal rat to regain some weight-bearing stepping capability, it appears that a sequence of specific proprioceptive inputs that are similar, but not identical, from step to step must be generated over repetitive step cycles. Furthermore, these cycles must include the activation of specific neural circuits that are intrinsic to the lumbosacral spinal cord segments. For these sensorimotor pathways to be effective in generating stepping, the spinal circuitry must be modulated to an appropriate excitability level. This level of modulation is sustained from supraspinal input in intact, but not spinal, rats. In a series of experiments with complete spinal rats, we have shown that an appropriate level of excitability of the spinal circuitry can be achieved using widely different means. For example, this modulation level can be acquired pharmacologically, via epidural electrical stimulation over specific lumbosacral spinal cord segments, and/or by use-dependent mechanisms such as step or stand training. Evidence as to how each of these treatments can "tune" the spinal circuitry to a "physiological state" that enables it to respond appropriately to proprioceptive input will be presented. We have found that each of these interventions can enable the proprioceptive input to actually control extensive details that define the dynamics of stepping over a range of speeds, loads, and directions. A series of experiments will be described that illustrate sensory control of stepping and standing after a spinal cord injury and the necessity for the "physiological state" of the spinal circuitry to be modulated within a critical window of excitability for this control to be manifested. The present findings have important consequences not only for our understanding of how the motor pattern for stepping is formed, but also for the design of rehabilitation intervention to restore lumbosacral circuit function in humans following a spinal cord injury.     

Surgical reconstruction of spinal cord circuit provides functional return in humans

This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron. Experimental data showed that most of the recovery depended on new growth reinnervating peripheral receptors. Restored sensory function and the return of spinal reflex was demonstrated by electrophysiology and functional magnetic resonance imaging of human cortex. This spinal cord surgery is a unique treatment of central nervous system injury resulting in useful functional return. Further improvements will not depend on surgical improvements. Adjuvant therapy aiming at ameliorating the activity in retinoic acid elements in dorsal root ganglion neurons could be a new therapeutic avenue in restoring spinal cord circuits after nerve root avulsion injury.     

Intraoperative neurophysiological monitoring of the spinal cord during spinal cord and spine surgery: a review focus on the corticospinal tracts.

Recent advances in technology and the refinement of neurophysiological methodologies are significantly changing intraoperative neurophysiological monitoring (IOM) of the spinal cord. This review will summarize the latest achievements in the monitoring of the spinal cord during spine and spinal cord surgeries. This overview is based on an extensive review of the literature and the authors' personal experience. Landmark articles and neurophysiological techniques have been briefly reported to contextualize the development of new techniques. This background is extended to describe the methodological approach to intraoperatively elicit and record spinal D wave and muscle motor evoked potentials (muscle MEPs). The clinical application of spinal D wave and muscle MEP recordings is critically reviewed (especially in the field of Neurosurgery) and new developments such as mapping of the dorsal columns and the corticospinal tracts are presented. In the past decade, motor evoked potential recording following transcranial electrical stimulation has emerged as a reliable technique to intraoperatively assess the functional integrity of the motor pathways. Criteria based on the absence/presence of potentials, their morphology and threshold-related parameters have been proposed for muscle MEPs. While the debate remains open, it appears that different criteria may be applied for different procedures according to the expected surgery-related morbidity and the ultimate goal of the surgeon (e.g. total tumor removal versus complete absence of transitory or permanent neurological deficits). On the other hand, D wave changes--when recordable--have proven to be the strongest predictors of maintained corticospinal tract integrity (and therefore, of motor function/recovery). Combining the use of muscle MEPs with D wave recordings provides the most comprehensive approach for assessing the functional integrity of the spinal cord motor tracts during surgery for intramedullary spinal cord tumors. However, muscle MEPs may suffice to assess motor pathways during other spinal procedures and in cases where the pathophysiology of spinal cord injury is purely ischemic. Finally, while MEPs are now considered the gold standard for monitoring the motor pathways, SEPs continue to retain value as they provide specificity for assessing the integrity of the dorsal column. However, we believe SEPs should not be used exclusively--or as an alternative to motor evoked potentials--during spine surgery, but rather as a complementary method in combination with MEPs. For intramedullary spinal tumor resection, SEPs should not be used exclusively without MEPs.     

Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study

Despite emerging contemporary biotechnological methods such as gene-and stem cell-based therapy,there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury.Our previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules,including vascular endothelial growth factor(VEGF),glial cell-line derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM) can improve morpho-functional recovery of injured spinal cord in rats and mini-pigs.To investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury,in this study,rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165,GDNF,NCAM1 at 4 hours after spinal cord injury.Three days after injury,epidural stimulations were given simultaneously above the lesion site at C5(to stimulate the cervical network related to forelimb functions) and below the lesion site at L2(to activate the central pattern generators) every other day for 4 weeks.Rats subjected to the combined treatment showed a limited functional improvement of the knee joint,high preservation of muscle fiber area in tibialis anterior muscle and increased H/M ratio in gastrocnemius muscle 30 days after spinal cord injury.However,beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters,and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene therapy.This study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy(VEGF,GDNF and NCAM) for treatment of spinal cord injury in rat models.The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.2.20.02.18) on February 20,2018.     

The origins of lumbosacral spinal evoked potentials in humans using a surface electrode recording technique.

Somatosensory evoked potentials were recorded over the lumbar spine and scalp in 12 normal subjects after stimulating the posterior tibial nerve at the knee and ankle and the sural nerve at the ankle. The H-reflex from the soleus muscle was recorded at the same time. The effects of stimulus intensity, frequency of stimulation and vibration were assessed. It was concluded that when the posterior tibial nerve was stimulated in the popliteal fossa, three negative peaks were recorded over the lumbosacral area. They arose from activity in the dorsal roots, the dorsal horn of the spinal cord (SD) and the ventral roots. In contrast when the posterior tibial nerve and the sural nerve were stimulated at the ankle only two negative peaks were recorded, a dorsal root potential and a spinal cord dorsum potential. In addition the data suggested that the peripheral nerve fibres that are involved with generating the surface recorded spinal potential with mixed nerve stimulation are primarily muscle afferents.     

Neuromuscular electrical stimulation in neurorehabilitation

This review provides a comprehensive overview of the clinical uses of neuromuscular electrical stimulation (NMES) for functional and therapeutic applications in subjects with spinal cord injury or stroke. Functional applications refer to the use of NMES to activate paralyzed muscles in precise sequence and magnitude to directly accomplish functional tasks. In therapeutic applications, NMES may lead to a specific effect that enhances function, but does not directly provide function. The specific neuroprosthetic or "functional" applications reviewed in this article include upper- and lower-limb motor movement for self-care tasks and mobility, respectively, bladder function, and respiratory control. Specific therapeutic applications include motor relearning, reduction of hemiplegic shoulder pain, muscle strengthening, prevention of muscle atrophy, prophylaxis of deep venous thrombosis, improvement of tissue oxygenation and peripheral hemodynamic functioning, and cardiopulmonary conditioning. Perspectives on future developments and clinical applications of NMES are presented.     

Repetetive hindlimb movement using intermittent adaptive neuromuscular electrical stimulation in an incomplete spinal cord injury rodent model

The long-term objective of this work is to understand the mechanisms by which electrical stimulation based movement therapies may harness neural plasticity to accelerate and enhance sensorimotor recovery after incomplete spinal cord injury (iSCI). An adaptive neuromuscular electrical stimulation (aNMES) paradigm was implemented in adult Long Evans rats with thoracic contusion injury (T8 vertebral level, 155 ± 2 Kdyne). In lengthy sessions with lightly anesthetized animals, hip flexor and extensor muscles were stimulated using an aNMES control system in order to generate desired hip movements. The aNMES control system, which used a pattern generator/pattern shaper structure, adjusted pulse amplitude to modulate muscle force in order to control hip movement. An intermittent stimulation paradigm was used (5-cycles/set; 20-second rest between sets; 100 sets). In each cycle, hip rotation caused the foot plantar surface to contact a stationary brush for appropriately timed cutaneous input. Sessions were repeated over several days while the animals recovered from injury. Results indicated that aNMES automatically and reliably tracked the desired hip trajectory with low error and maintained range of motion with only gradual increase in stimulation during the long sessions. Intermittent aNMES thus accounted for the numerous factors that can influence the response to NMES: electrode stability, excitability of spinal neural circuitry, non-linear muscle recruitment, fatigue, spinal reflexes due to cutaneous input, and the endogenous recovery of the animals. This novel aNMES application in the iSCI rodent model can thus be used in chronic stimulation studies to investigate the mechanisms of neuroplasticity targeted by NMES-based repetitive movement therapy.