Bladder Responses to Thoracolumbar Epidural Stimulation in Female Urethane-Anesthetized Rats with Graded Contusion Spinal Cord Injuries.

Spinal cord epidural stimulation (scES) is a therapeutic option that promotes functional improvements in sensory, motor, and autonomic functions following spinal cord injury (SCI). Previous scES mapping studies targeting the lower urinary tract (LUT) in rats demonstrated functional response variability based upon lumbosacral level, parameters used, extent of injury (spinally intact vs. chronic anatomically complete spinal transections), and sex. In the current study, female rats with clinically relevant graded incomplete T9 contusion injuries were mapped with scES at 60 days post-injury at three spinal levels (T13, L3, L6) with a novel miniature 15-electrode array designed to deliver optimal specificity. The results obtained during bladder fill and void cycles conducted under urethane anesthesia indicate frequency dependent sub-motor threshold effects on LUT function with a single row of electrodes positioned across the full medio-lateral extent of the dorsal cord. The findings of improved storage and emptying, represented by significantly longer inter-contractile intervals with T13 scES and L3 scES and by a significantly increased estimated void efficiency with L6 scES, respectively, are consistent with previous studies using intact and chronic complete transected male and female rats. The data support the efficacy of selective spinal network stimulation to drive functionally relevant networks for storage versus emptying phases of the urinary cycle. The current findings further demonstrate the translational promise of scES for SCI individuals with LUT dysfunctions, regardless of injury severity.

Effects of Robotic Postural Stand Training with Epidural Stimulation on Sitting Postural Control in Individuals with Spinal Cord Injury: A Pilot Study.

(1) Background. High-level spinal cord injury (SCI) disrupts trunk control, leading to an impaired performance of upright postural tasks in sitting and standing. We previously showed that a novel robotic postural stand training with spinal cord epidural stimulation targeted at facilitating standing (Stand-scES) largely improved standing trunk control in individuals with high-level motor complete SCI. Here, we aimed at assessing the effects of robotic postural stand training with Stand-scES on sitting postural control in the same population. (2) Methods. Individuals with cervical (n = 5) or high-thoracic (n = 1) motor complete SCI underwent approximately 80 sessions (1 h/day; 5 days/week) of robotic postural stand training with Stand-scES, which was performed with free hands (i.e., without using handlebars) and included periods of standing with steady trunk control, self-initiated trunk and arm movements, and trunk perturbations. Sitting postural control was assessed on a standard therapy mat, with and without scES targeted at facilitating sitting (Sit-scES), before and after robotic postural stand training. Independent sit time and trunk center of mass (CM) displacement were assessed during a 5 min time window to evaluate steady sitting control. Self-initiated antero-posterior and medial-lateral trunk movements were also attempted from a sitting position, with the goal of covering the largest distance in the respective cardinal directions. Finally, the four Neuromuscular Recovery Scale items focused on sitting trunk control (Sit, Sit-up, Trunk extension in sitting, Reverse sit-up) were assessed. (3) Results. In summary, neither statistically significant differences nor large Effect Size were promoted by robotic postural stand training for the sitting outcomes considered for analysis. (4) Conclusions. The findings of the present study, together with previous observations, may suggest that robotic postural stand training with Stand-scES promoted trunk motor learning that was posture- and/or task-specific and, by itself, was not sufficient to significantly impact sitting postural control.

Robotic Postural Training With Epidural Stimulation for the Recovery of Upright Postural Control in Individuals With Motor Complete Spinal Cord Injury: A Pilot Study.

Activity-based training and lumbosacral spinal cord epidural stimulation (scES) have the potential to restore standing and walking with self-balance assistance after motor complete spinal cord injury (SCI). However, improvements in upright postural control have not previously been addressed in this population. Here, we implemented a novel robotic postural training with scES, performed with free hands, to restore upright postural control in individuals with chronic, cervical (n = 5) or high-thoracic (n = 1) motor complete SCI, who had previously undergone stand training with scES using a walker or a standing frame for self-balance assistance. Robotic postural training re-enabled and/or largely improved the participants' ability to control steady standing, self-initiated trunk movements and upper limb reaching movements while standing with free hands, receiving only external assistance for pelvic control. These improvements were associated with neuromuscular activation pattern adaptations above and below the lesion. These findings suggest that the human spinal cord below the level of injury can generate meaningful postural responses when its excitability is modulated by scES, and can learn to improve these responses. Upright postural control improvements can enhance functional motor recovery promoted by scES after severe SCI.

Standing Reactive Postural Responses of Lower Limbs With and Without Self-Balance Assistance in Individuals With Spinal Cord Injury Receiving Epidural Stimulation.

Spinal cord epidural stimulation can promote the recovery of motor function in individuals with severe spinal cord injury (SCI) by enabling the spinal circuitry to interpret sensory information and generate related neuromuscular responses. This approach enables the spinal cord to generate lower limb extension patterns during weight bearing, allowing individuals with SCI to achieve upright standing. We have shown that the human spinal cord can generate some standing postural responses during self-initiated body weight shifting. In this study, we investigated the ability of individuals with motor complete SCI receiving epidural stimulation to generate standing reactive postural responses after external perturbations were applied at the trunk. A cable-driven robotic device was used to provide constant assistance for pelvic control and to deliver precise trunk perturbations while participants used their hands to grasp onto handlebars for self-balance support (hands-on) as well as when participants were without support (free-hands). Five individuals with motor complete SCI receiving lumbosacral spinal cord epidural stimulation parameters specific for standing (Stand-scES) participated in this study. Trunk perturbations (average magnitude: 17 ± 3% body weight) were delivered randomly in the four cardinal directions. Participants attempted to control each perturbation such that upright standing was maintained and no additional external assistance was needed. Lower limb postural responses were generally more frequent, larger in magnitude, and appropriately modulated during the free-hands condition. This was associated with trunk displacement and lower limb loading modulation that were larger in the free-hands condition. Further, we observed discernible lower limb muscle synergies that were similar between the two perturbed standing conditions. These findings suggest that the human spinal circuitry involved in postural control retains the ability to generate meaningful lower limb postural responses after SCI when its excitability is properly modulated. Moreover, lower limb postural responses appear enhanced by a standing environment without upper limb stabilization that promotes afferent inputs associated with a larger modulation of ground reaction forces and trunk kinematics. These findings should be considered when developing future experimental frameworks aimed at studying upright postural control and activity-based recovery training protocols aimed at promoting neural plasticity and sensory-motor recovery.

Spinal Cord Epidural Stimulation Improves Lower Spine Sitting Posture Following Severe Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) leads to impaired trunk motor control, negatively impacting the performance of activities of daily living in the affected individuals. Improved trunk control with better sitting posture has been previously observed due to neuromuscular electrical stimulation and transcutaneous spinal stimulation, while improved postural stability has been observed with spinal cord epidural stimulation (scES). Hence, we studied how trunk-specific scES impacts sitting independence and posture. Fourteen individuals with chronic, severe cervical SCI with an implanted neurostimulator performed a 5-min tall-sit task without and with trunk-specific scES. Spine posture was assessed by placing markers on five spine levels and evaluating vertical spine inclination angles. Duration of trunk manual assistance was used to assess independence along with the number of independence changes and average independence score across those changes. With scES, the sacrum-L1 inclination and number of independence changes tended to decrease by 1.64 ± 3.16° (p = 0.07; Cohen's d = 0.53) and 9.86 ± 16.8 (p = 0.047; Cohen's d = 0.59), respectively. Additionally, for the participants who had poor sitting independence without scES, level of independence tended to increase by 12.91% [0%, 31.52%] (p = 0.38; Cohen's d = 0.96) when scES was present. Hence, trunk-specific scES promoted improvements in lower spine posture and lower levels of trunk assistance.

Case study: persistent recovery of hand movement and tactile sensation in peripheral nerve injury using targeted transcutaneous spinal cord stimulation.

Peripheral nerve injury can lead to chronic pain, paralysis, and loss of sensation, severely affecting quality of life. Spinal cord stimulation has been used in the clinic to provide pain relief arising from peripheral nerve injuries, however, its ability to restore function after peripheral nerve injury have not been explored. Neuromodulation of the spinal cord through transcutaneous spinal cord stimulation (tSCS), when paired with activity-based training, has shown promising results towards restoring volitional limb control in people with spinal cord injury. We show, for the first time, the effectiveness of targeted tSCS in restoring strength (407% increase from 1.79 ± 1.24 N to up to 7.3 ± 0.93 N) and significantly increasing hand dexterity in an individual with paralysis due to a peripheral nerve injury (PNI). Furthermore, this is the first study to document a persisting 3-point improvement during clinical assessment of tactile sensation in peripheral injury after receiving 6 weeks of tSCS. Lastly, the motor and sensory gains persisted for several months after stimulation was received, suggesting tSCS may lead to long-lasting benefits, even in PNI. Non-invasive spinal cord stimulation shows tremendous promise as a safe and effective therapeutic approach with broad applications in functional recovery after debilitating injuries.

Artifact Adaptive Ideal Filtering of EMG Signals Contaminated by Spinal Cord Transcutaneous Stimulation.

The aims of this study are to characterize the contamination of EMG signals by artifacts generated by the delivery of spinal cord transcutaneous stimulation (scTS) and to evaluate the performance of an Artifact Adaptive Ideal Filtering (AA-IF) technique to remove scTS artifacts from EMG signals. METHODS: In five participants with spinal cord injury (SCI), scTS was delivered at different combinations of intensity (from 20 to 55 mA) and frequencies (from 30 to 60 Hz) while Biceps Brachii (BB) and Triceps Brachii (TB) muscles were at rest or voluntarily activated. Using a Fast Fourier Transform (FFT), we characterized peak amplitude of scTS artifacts and boundaries of contaminated frequency bands in the EMG signals recorded from BB and TB muscles. Then, we applied the AA-IF technique and the empirical mode decomposition Butterworth filtering method (EMD-BF) to identify and remove scTS artifacts. Finally, we compared the content of the FFT that was preserved and the root mean square of the EMG signals (EMGrms) following application of the AA-IF and EMD-BF techniques. RESULTS: Frequency bands of ~2Hz width were contaminated by scTS artifact at frequencies nearby the main frequency set for the stimulator and its harmonics. The width of the frequency bands contaminated by scTS artifacts increased with current intensity delivered using scTS ( [Formula: see text]), was lower when EMG signals were recorded during voluntary contractions compared to rest ( [Formula: see text]), and was larger in BB muscle compared to TB muscle ( [Formula: see text]). A larger portion of the FFT was preserved using the AA-IF technique compared to the EMD-BF technique (96±5% vs. 75±6%, [Formula: see text]). CONCLUSION: The AA-IF technique allows for a precise identification of the frequency bands contaminated by scTS artifacts and ultimately preserves a larger amount of uncontaminated content from the EMG signals.

Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats.

Recent pre-clinical and clinical spinal cord epidural stimulation (scES) experiments specifically targeting the thoracolumbar and lumbosacral circuitries mediating lower urinary tract (LUT) function have shown improvements in storage, detrusor pressure, and emptying. With the existence of a lumbar spinal coordinating center in rats that is involved with external urethral sphincter (EUS) functionality during micturition, the mid-lumbar spinal cord (specifically L3) was targeted in the current study with scES to determine if the EUS and thus the void pattern could be modulated, using both intact and chronic complete spinal cord injured female rats under urethane anesthesia. L3 scES at select frequencies and intensities of stimulation produced a reduction in void volumes and EUS burst duration in intact rats. After chronic transection, three different subgroups of LUT dysfunction were identified and the response to L3 scES promoted different cystometry outcomes, including changes in EUS bursting. The current findings suggest that scES at the L3 level can generate functional neuromodulation of both the urinary bladder and the EUS in intact and SCI rats to enhance voiding in a variety of clinical scenarios.

Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Robotic upright stand trainer (RobUST) and postural control in individuals with spinal cord injury.

CONTEXT/OBJECTIVE: Assessed feasibility and potential effectiveness of using a novel robotic upright stand trainer (RobUST) to deliver postural perturbations or provide assistance-as-needed at the trunk while individuals with spinal cord injury (SCI) performed stable standing and self-initiated trunk movements. These tasks were assessed with research participants' hands on handlebars for self-balance assistance (hands on) and with hands off (free hands). DESIGN: Proof of concept study. PARTICIPANTS: Four individuals with motor complete (n = 3) or incomplete (n = 1) SCI who were not able to achieve independent standing and presented a neurological lesion level ranging from cervical 4 to thoracic 2. OUTCOME MEASURES: Ground reaction forces, trunk displacement, and electromyography activity of trunk and lower limb muscles. RESULTS: Research participants received continuous pelvic assistance via RobUST, and manual trainer assistance at the knees to maintain standing. Participants were able to attempt all tasks. Free hands trunk perturbations resulted in greater load bearing-related sensory information (73% ipsilateral vertical loading), trunk displacement (57%), and muscle activation compared to hands on. Similarly, free hands stable standing with RobUST assistance-as-needed resulted in 8.5% larger bodyweight bearing, 112% larger trunk movement velocity, and higher trunk muscles activation compared to standing with hands on. Self-initiated trunk movements controlled by hands on showed 116% greater trunk displacement, 10% greater vertical ground reaction force, and greater ankle muscle activation compared to free hands. CONCLUSION: RobUST established a safe and challenging standing environment for individuals with SCI and has the potential to improve training paradigms and assessments of standing postural control.

Intrathecal and Oral Baclofen Use in Adults With Spinal Cord Injury: A Systematic Review of Efficacy in Spasticity Reduction, Functional Changes, Dosing, and Adverse Events.

OBJECTIVE: To examine the efficacy, dosing, and safety profiles of intrathecal and oral baclofen in treating spasticity after spinal cord injury (SCI). DATA SOURCES: PubMed and Cochrane Databases were searched from 1970-2018 with keywords baclofen, spinal cord injury, and efficacy. STUDY SELECTION: The database search yielded 588 sources and 10 additional relevant publications. After removal of duplicates, 398 publications were screened. DATA EXTRACTION: Data were extracted using the following population, intervention, comparator, outcomes, and study designs criteria: studies including adult patients with SCI with spasticity; the intervention could be oral or intrathecal administration of baclofen; selection was inclusive for control groups, surgical management, rehabilitation, and alternative pharmaceutical agents; outcomes were efficacy, dosing, and adverse events. Randomized controlled trials, observational studies, and case reports were included. Meta-analyses and systematic reviews were excluded. DATA SYNTHESIS: A total of 98 studies were included with 1943 patients. Only 4 randomized, double-blinded, and placebo-controlled trials were reported. Thirty-nine studies examined changes in the Modified Ashworth Scale (MAS; 34 studies) and Penn Spasm scores (Penn Spasm Frequency; 19 studies), with average reductions of 1.7±1.3 and 1.6±1.4 in individuals with SCI, respectively. Of these data, a total of 6 of the 34 studies (MAS) and 2 of the 19 studies (Penn Spasm Frequency) analyzed oral baclofen. Forty-three studies addressed adverse events with muscle weakness and fatigue frequently reported. CONCLUSIONS: Baclofen is the most commonly-prescribed antispasmodic after SCI. Surprisingly, there remains a significant lack of large, placebo-controlled, double-blinded clinical trials, with most efficacy data arising from small studies examining treatment across different etiologies. In the studies reviewed, baclofen effectively improved spasticity outcome measures, with increased efficacy through intrathecal administration. Few studies assessed how reduced neural excitability affected residual motor function and activities of daily living. A host of adverse events were reported that may negatively affect quality of life. Comparative randomized controlled trials of baclofen and alternative treatments are warranted because these have demonstrated promise in relieving spasticity with reduced adverse events and without negatively affecting residual motor function.

Modular organization of locomotor networks in people with severe spinal cord injury.

Introduction: Previous studies support modular organization of locomotor circuitry contributing to the activation of muscles in a spatially and temporally organized manner during locomotion. Human spinal circuitry may reorganize after spinal cord injury; however, it is unclear if reorganization of spinal circuitry post-injury affects the modular organization. Here we characterize the modular synergy organization of locomotor muscle activity expressed during assisted stepping in subjects with complete and incomplete spinal cord injury (SCI) of varying chronicity, before any explicit training regimen. We also investigated whether the synergy characteristics changed in two subjects who achieved independent walking after training with spinal cord epidural stimulation. Methods: To capture synergy structures during stepping, individuals with SCI were stepped on a body-weight supported treadmill with manual facilitation, while electromyography (EMGs) were recorded from bilateral leg muscles. EMGs were analyzed using non-negative matrix factorization (NMF) and independent component analysis (ICA) to identify synergy patterns. Synergy patterns from the SCI subjects were compared across different clinical characteristics and to non-disabled subjects (NDs). Results: Results for both NMF and ICA indicated that the subjects with SCI were similar among themselves, but expressed a greater variability in the number of synergies for criterion variance capture compared to NDs, and weaker correlation to NDs. ICA yielded a greater number of muscle synergies than NMF. Further, the clinical characteristics of SCI subjects and chronicity did not predict any significant differences in the spatial synergy structures despite any neuroplastic changes. Further, post-training synergies did not become closer to ND synergies in two individuals. Discussion: These findings suggest fundamental differences between motor modules expressed in SCIs and NDs, as well as a striking level of spatial and temporal synergy stability in motor modules in the SCI population, absent the application of specific interventions.

Targeting bladder function with network-specific epidural stimulation after chronic spinal cord injury.

Profound dysfunctional reorganization of spinal networks and extensive loss of functional continuity after spinal cord injury (SCI) has not precluded individuals from achieving coordinated voluntary activity and gaining multi-systemic autonomic control. Bladder function is enhanced by approaches, such as spinal cord epidural stimulation (scES) that modulates and strengthens spared circuitry, even in cases of clinically complete SCI. It is unknown whether scES parameters specifically configured for modulating the activity of the lower urinary tract (LUT) could improve both bladder storage and emptying. Functional bladder mapping studies, conducted during filling cystometry, identified specific scES parameters that improved bladder compliance, while maintaining stable blood pressure, and enabled the initiation of voiding in seven individuals with motor complete SCI. Using high-resolution magnetic resonance imaging and finite element modeling, specific neuroanatomical structures responsible for modulating bladder function were identified and plotted as heat maps. Data from this pilot clinical trial indicate that scES neuromodulation that targets bladder compliance reduces incidences of urinary incontinence and provides a means for mitigating autonomic dysreflexia associated with bladder distention. The ability to initiate voiding with targeted scES is a key step towards regaining volitional control of LUT function, advancing the application and adaptability of scES for autonomic function.

Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

Pre-clinical studies have shown that spinal cord epidural stimulation (scES) at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel. The current mapping experiments were conducted to investigate scES efficacy at the level of hypogastric nerve inputs/outputs (T13-L2) in male and female rats under urethane anesthesia. As found with L5-S1 scES, T13-L2 scES at select frequencies and intensities of stimulation produced an increase in inter-contraction interval (ICI) in non-injured female rats but a short-latency void in chronic T9 transected rats, as well as reduced rectal activity in all groups. However, the detrusor pressure during the lengthened ICI (i.e., urinary hold) remained at a low pressure and was not elevated as seen with L5-S1 scES, an effect that's critical for translation to the clinic as high fill pressures can damage the kidneys. Furthermore, T13-L2 scES was shown to stimulate voiding post-transection by increasing bladder activity while also directly inhibiting the external urethral sphincter, a pattern necessary to overcome detrusor-sphincter dyssynergia. Additionally, select scES parameters at T13-L2 also increased distal colon activity in all groups. Together, the current findings suggest that optimization of scES for bladder and bowel will likely require multiple electrode cohorts at different locations that target circuitries coordinating sympathetic, parasympathetic and somatic outputs.

Spinal cord imaging markers and recovery of standing with epidural stimulation in individuals with clinically motor complete spinal cord injury.

Spinal cord epidural stimulation (scES) is an intervention to restore motor function in those with severe spinal cord injury (SCI). Spinal cord lesion characteristics assessed via magnetic resonance imaging (MRI) may contribute to understand motor recovery. This study assessed relationships between standing ability with scES and spared spinal cord tissue characteristics at the lesion site. We hypothesized that the amount of lateral spared cord tissue would be related to independent extension in the ipsilateral lower limb. Eleven individuals with chronic, clinically motor complete SCI underwent spinal cord MRI, and were subsequently implanted with scES. Standing ability and lower limb activation patterns were assessed during an overground standing experiment with scES. This assessment occurred prior to any activity-based intervention with scES. Lesion hyperintensity was segmented from T2 axial images, and template-based analysis was used to estimate spared tissue in anterior, posterior, right, and left spinal cord regions. Regression analysis was used to assess relationships between imaging and standing outcomes. Total volume of spared tissue was related to left (p = 0.007), right (p = 0.005), and bilateral (p = 0.011) lower limb extension. Spared tissue in the left cord region was related to left lower limb extension (p = 0.019). A positive trend (p = 0.138) was also observed between right spared cord tissue and right lower limb extension. In this study, MRI measures of spared spinal cord tissue were significantly related to standing outcomes with scES. These preliminary results warrant future investigation of roles of supraspinal input and MRI-detected spared spinal cord tissue on lower limb motor responsiveness to scES.

Recruitment order of motor neurons promoted by epidural stimulation in individuals with spinal cord injury.

Spinal cord epidural stimulation (scES) combined with activity-based training can promote motor function recovery in individuals with motor complete spinal cord injury (SCI). The characteristics of motor neuron recruitment, which influence different aspects of motor control, are still unknown when motor function is promoted by scES. Here, we enrolled five individuals with chronic motor complete SCI implanted with an scES unit to study the recruitment order of motor neurons during standing enabled by scES. We recorded high-density electromyography (HD-EMG) signals on the vastus lateralis muscle and inferred the order of recruitment of motor neurons from the relation between amplitude and conduction velocity of the scES-evoked EMG responses along the muscle fibers. Conduction velocity of scES-evoked responses was modulated over time, whereas stimulation parameters and standing condition remained constant, with average values ranging between 3.0 ± 0.1 and 4.4 ± 0.3 m/s. We found that the human spinal circuitry receiving epidural stimulation can promote both orderly (according to motor neuron size) and inverse trends of motor neuron recruitment, and that the engagement of spinal networks promoting rhythmic activity may favor orderly recruitment trends. Conversely, the different recruitment trends did not appear to be related with time since injury or scES implant, nor to the ability to achieve independent knees extension, nor to the conduction velocity values. The proposed approach can be implemented to investigate the effects of stimulation parameters and training-induced neural plasticity on the characteristics of motor neuron recruitment order, contributing to improve mechanistic understanding and effectiveness of epidural stimulation-promoted motor recovery after SCI.NEW & NOTEWORTHY After motor complete spinal cord injury, the human spinal cord receiving epidural stimulation can promote both orderly and inverse trends of motor neuron recruitment. The engagement of spinal networks involved in the generation of rhythmic activity seems to favor orderly recruitment trends.

Bladder and bowel responses to lumbosacral epidural stimulation in uninjured and transected anesthetized rats.

Spinal cord epidural stimulation (scES) mapping at L5-S1 was performed to identify parameters for bladder and bowel inhibition and/or contraction. Using spinally intact and chronic transected rats of both sexes in acute urethane-anesthetized terminal preparations, scES was systematically applied using a modified Specify 5-6-5 (Medtronic) electrode during bladder filling/emptying cycles while recording bladder and colorectal pressures and external urethral and anal sphincter electromyography activity. The results indicate frequency-dependent effects on void volume, micturition, bowel peristalsis, and sphincter activity just above visualized movement threshold intensities that differed depending upon neurological intactness, with some sex-dependent differences. Thereafter, a custom-designed miniature 15-electrode array designed for greater selectivity was tested and exhibited the same frequency-dependent urinary effects over a much smaller surface area without any concurrent movements. Thus, select activation of autonomic nervous system circuitries with scES is a promising neuromodulation approach for expedient translation to individuals with SCI and potentially other neurologic disorders.

Effect of Different Forms of Activity-Based Recovery Training on Bladder, Bowel, and Sexual Function After Spinal Cord Injury.

OBJECTIVES: To investigate whether the urogenital and bowel functional gains previously demonstrated post-locomotor step training after chronic spinal cord injury could have been derived due to weight-bearing alone or from exercise in general. DESIGN: Prospective cohort study; pilot trial with small sample size. SETTING: Urogenital and bowel scientific core facility at a rehabilitation institute and spinal cord injury research center in the United States. PARTICIPANTS: Men and women (N=22) with spinal cord injury (American Spinal Injury Association Impairment Scale grades of A-D) participated in this study. INTERVENTIONS: Approximately 80 daily 1-hour sessions of either stand training or nonweight-bearing arm crank ergometry. Comparisons were made with previously published locomotor training data (step; N=7). MAIN OUTCOME MEASURES: Assessments at both pre- and post-training timepoints included cystometry for bladder function and International Data Set Questionnaires for bowel and sexual functions. RESULTS: Cystometry measurements revealed a significant decrease in bladder pressure and limited improvement in compliance with nonweight-bearing exercise but not with standing. Although International Data Set questionnaires revealed profound bowel dysfunction and marked deficits in sexual function pretraining, no differences were identified poststand or after nonweight-bearing exercise. CONCLUSIONS: These pilot trial results suggest that, although stand and weight-bearing alone do not benefit pelvic organ functions after spinal cord injury, exercise in general may contribute at least partially to the lowering of bladder pressure and the increase in compliance that was seen previously with locomotor training, potentially through metabolic, humoral, and/or cardiovascular mechanisms. Thus, to maximize activity-based recovery training benefits for functions related to storage and emptying, an appropriate level of sensory input to the spinal cord neural circuitries controlling bladder and bowel requires task-specific stepping.