Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation.

OBJECTIVE: Physical therapists develop patient-centered exercise prescriptions to help overcome the physical, emotional, psychosocial, and environmental stressors that undermine a person's health. Optimally prescribing muscle activity for people with disability, such as a spinal cord injury, is challenging because of their loss of volitional movement control and the deterioration of their underlying skeletal systems. This report summarizes spinal cord injury-specific factors that should be considered in patient-centered, precision prescription of muscle activity for people with spinal cord injury. This report also presents a muscle genomic and epigenomic analysis to examine the regulation of the proliferator-activated receptor γ coactivator 1α (PGC-1α) (oxidative) and myostatin (hypertrophy) signaling pathways in skeletal muscle during low-frequency (lower-force) electrically induced exercise versus higher-frequency (higher-force) electrically induced exercise under constant muscle recruitment (intensity). METHODS: Seventeen people with spinal cord injury participated in 1 or more unilateral electrically induced exercise sessions using a lower-force (1-, 3-, or 5-Hz) or higher-force (20-Hz) protocol. Three hours after the exercise session, percutaneous muscle biopsies were performed on exercised and nonexercised muscles for genomic and epigenomic analysis. RESULTS: We found that low-frequency (low-force) electrically induced exercise significantly increased the expression of PGC-1α and decreased the expression of myostatin, consistent with the expression changes observed with high-frequency (higher-force) electrically induced exercise. Further, we found that low-frequency (lower-force) electrically induced exercise significantly demethylated, or epigenetically promoted, the PGC-1α signaling pathway. A global epigenetic analysis showed that >70 pathways were regulated with low-frequency (lower-force) electrically induced exercise. CONCLUSION: These novel results support the notion that low-frequency (low-force) electrically induced exercise may offer a more precise rehabilitation strategy for people with chronic paralysis and severe osteoporosis. Future clinical trials are warranted to explore whether low-frequency (lower-force) electrically induced exercise training affects the overall health of people with chronic spinal cord injury.

Meeting Proceedings for SCI 2020: Launching a Decade of Disruption in Spinal Cord Injury Research.

The spinal cord injury (SCI) research community has experienced great advances in discovery research, technology development, and promising clinical interventions in the past decade. To build upon these advances and maximize the benefit to persons with SCI, the National Institutes of Health (NIH) hosted a conference February 12-13, 2019 titled "SCI 2020: Launching a Decade of Disruption in Spinal Cord Injury Research." The purpose of the conference was to bring together a broad range of stakeholders, including researchers, clinicians and healthcare professionals, persons with SCI, industry partners, regulators, and funding agency representatives to break down existing communication silos. Invited speakers were asked to summarize the state of the science, assess areas of technological and community readiness, and build collaborations that could change the trajectory of research and clinical options for people with SCI. In this report, we summarize the state of the science in each of five key domains and identify the gaps in the scientific literature that need to be addressed to move the field forward.

Hybrid stimulation enhances torque as a function of muscle fusion in human paralyzed and non-paralyzed skeletal muscle.

OBJECTIVE: After spinal cord injury (SCI), hybrid stimulation patterns that interpose paired-pulse doublets over a constant-frequency background may enhance the metabolic "work" (muscle torque) performed by paralyzed muscle. This study examined the effect of background stimulation frequency on the torque contribution of the doublet before and after fatigue. DESIGN: Cross-sectional study. SETTING: Research laboratory in an academic medical center. PARTICIPANTS: Five men with chronic sensory and motor-complete SCI and ten non-SCI controls (6 males, 4 females). SCI subjects were recruited from a long-term study of unilateral plantar-flexor training; both limbs were tested for the present study. INTERVENTIONS: Subjects underwent plantar flexor stimulation at 5, 7, 9, and 12 Hz. The four background frequencies were overlaid with 6 ms doublets delivered at the start, middle, or at both the start and middle of each train. The 5 Hz and 12 Hz frequencies were analyzed after fatigue. OUTCOME MEASURES: Mean torque, peak torque, torque fusion index, doublet torque. RESULTS: Trains with doublets at both the start and middle yielded the most consistent enhancement of torque (all P < 0.028). Torque contribution of the doublet was greatest at low stimulus frequencies (all P < 0.016). The low relative fusion of untrained paralyzed muscle preserved the efficacy of the doublet even during fatigue. CONCLUSION: Hybrid stimulus trains may be an effective way to increase contractile work in paralyzed muscle, even after fatigue. They may be useful for rehabilitation strategies designed to enhance the metabolic work performed by paralyzed skeletal muscle.

Physiotherapy education is a good financial investment, up to a certain level of student debt: an inter-professional economic analysis.

QUESTIONS: What is the economic value of a physiotherapy career relative to other healthcare professions? Is the graduate debt reported for physiotherapy manageable according to recommended salary-weighted debt service ratio benchmarks? DESIGN: Net present value (NPV) is an economic modelling approach that compares costs and benefits of an investment such as healthcare education. An economic analysis using the NPV approach was conducted and reported in US dollars for the Doctor of Physical Therapy degree. Comparable calculations were made for a range of other healthcare qualifications. Debt service ratios were also calculated under a range of scenarios. OUTCOME MEASURES: Entry-level salaries and rate of salary growth were obtained from government databases. Student debt levels were obtained from published sources. Because no national estimate exists for physical therapy student debt, debt was modelled for recent Doctor of Physical Therapy (DPT) graduates and for several hypothetical debt tiers. The NPV modelled future physical therapy earnings less the cost of education and the opportunity cost of foregone earnings from alternate careers. RESULTS: At the debt level reported by recent graduates (US $86563), physical therapy NPV was higher than occupational therapy, optometry, veterinary medicine, and chiropractic but lower than dentistry, pharmacy, nurse practitioner, physician assistant, and all medical specialties. At $150000 debt, physical therapy NPV falls below all careers except veterinary medicine and chiropractic. Students with>$200000 debt may not achieve recommended repayment benchmarks. At high debt levels (>$266000), physical therapy NPV no longer exceeds that of a bachelor's degree. CONCLUSION: Physiotherapy education is a good financial investment, up to a certain level of student debt. Students should carefully consider the amount of debt they are willing to incur in order to pursue a physiotherapy career. Likewise, physiotherapy education programs should consider the role they may play in bolstering the economic value of their graduates' future careers. [Shields RK, Dudley-Javoroski S (2018) Physiotherapy education is a good financial investment, up to a certain level of student debt: an inter-professional economic analysis. Journal of Physiotherapy 64: 182-190].

Low-Force Muscle Activity Regulates Energy Expenditure after Spinal Cord Injury.

Reduced physical activity is a primary risk factor for increased morbidity and mortality. People with spinal cord injury (SCI) have reduced activity for a lifetime, as they cannot volitionally activate affected skeletal muscles. We explored whether low-force and low-frequency stimulation is a viable strategy to enhance systemic energy expenditure in people with SCI. PURPOSE: This study aimed to determine the effects of low stimulation frequency (1 and 3 Hz) and stimulation intensity (50 and 100 mA) on energy expenditure in people with SCI. We also examined the relationship between body mass index and visceral adipose tissue on energy expenditure during low-frequency stimulation. METHODS: Ten individuals with complete SCI underwent oxygen consumption monitoring during electrical activation of the quadriceps and hamstrings at 1 and 3 Hz and at 50 and 100 mA. We calculated the difference in energy expenditure between stimulation and rest and estimated the number of days that would be necessary to burn 1 lb of body fat (3500 kcal) for each stimulation protocol (1 vs 3 Hz). RESULTS: Both training frequencies induced a significant increase in oxygen consumption above a resting baseline level (P < 0.05). Energy expenditure positively correlated with stimulus intensity (muscle recruitment) and negatively correlated with adiposity (reflecting the insulating properties of adipose tissue). We estimated that 1 lb of body fat could be burned more quickly with 1 Hz training (58 d) as compared with 3 Hz training (87 d) if an identical number of pulses were delivered. CONCLUSION: Low-frequency stimulation increased energy expenditure per pulse and may be a feasible option to subsidize physical activity to improve metabolic status after SCI.

Low-frequency stimulation regulates metabolic gene expression in paralyzed muscle.

The altered metabolic state after a spinal cord injury compromises systemic glucose regulation. Skeletal muscle atrophies and transforms into fast, glycolytic, and insulin-resistant tissue. Osteoporosis is common after spinal cord injury and limits the ability to exercise paralyzed muscle. We used a novel approach to study the acute effect of two frequencies of stimulation (20 and 5 Hz) on muscle fatigue and gene regulation in people with chronic paralysis. Twelve subjects with chronic (>1 yr) and motor complete spinal cord injury (ASIA A) participated in the study. We assessed the twitch force before and after a single session of electrical stimulation (5 or 20 Hz). We controlled the total number of pulses delivered for each protocol (10,000 pulses). Three hours after the completion of the electrical stimulation (5 or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodeling. We discovered that the 5-Hz stimulation session induced a similar amount of fatigue and a five- to sixfold increase (P < 0.05) in key metabolic transcription factors, including PGC-1α, NR4A3, and ABRA as the 20-Hz session. Neither session showed a robust regulation of genes for glycolysis, oxidative phosphorylation, or mitochondria remodeling. We conclude that a low-force and low-frequency stimulation session is effective at inducing fatigue and regulating key metabolic transcription factors in human paralyzed muscle. This strategy may be an acceptable intervention to improve systemic metabolism in people with chronic paralysis.

A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury.

Paralysis after a spinal cord injury (SCI) induces physiological adaptations that compromise the musculoskeletal and metabolic systems. Unlike non-SCI individuals, people with spinal cord injury experience minimal muscle activity which compromises optimal glucose utilization and metabolic control. Acute or chronic muscle activity, induced through electrical stimulation, may regulate key genes that enhance oxidative metabolism in paralyzed muscle. We investigated the short and long term effects of electrically induced exercise on mRNA expression of human paralyzed muscle. We developed an exercise dose that activated the muscle for only 0.6% of the day. The short term effects were assessed 3 hours after a single dose of exercise, while the long term effects were assessed after training 5 days per week for at least one year (adherence 81%). We found a single dose of exercise regulated 117 biological pathways as compared to 35 pathways after one year of training. A single dose of electrical stimulation increased the mRNA expression of transcriptional, translational, and enzyme regulators of metabolism important to shift muscle toward an oxidative phenotype (PGC-1α, NR4A3, IFRD1, ABRA, PDK4). However, chronic training increased the mRNA expression of specific metabolic pathway genes (BRP44, BRP44L, SDHB, ACADVL), mitochondrial fission and fusion genes (MFF, MFN1, MFN2), and slow muscle fiber genes (MYH6, MYH7, MYL3, MYL2). These findings support that a dose of electrical stimulation (∼10 minutes/day) regulates metabolic gene signaling pathways in human paralyzed muscle. Regulating these pathways early after SCI may contribute to reducing diabetes in people with longstanding paralysis from SCI.

Active-resisted stance modulates regional bone mineral density in humans with spinal cord injury.

OBJECTIVE: In people with spinal cord injury (SCI), active-resisted stance using electrical stimulation of the quadriceps delivered a therapeutic stress to the femur (∼150% of body weight) and attenuated bone mineral density (BMD) decline. In standard densitometry protocols, BMD is averaged over the entire bone cross-section. An asymmetric adaptation to mechanical load may be masked by non-responding regions. The purpose of this study was to test a novel method to assess regional BMD of the femur in individuals with SCI. We hypothesize that there will be regional bone-sparing changes as a result of active-resisted stance. DESIGN: Mixed cross-sectional and longitudinal. SETTING: Research laboratory. PARTICIPANTS: Twelve individuals with SCI and twelve non-SCI controls. INTERVENTION: Individuals with SCI experienced active-resisted stance or passive stance for up to 3 years. OUTCOME MEASURES: Peripheral quantitative computed tomography images from were partitioned so that femur anatomic quadrants could be separately analyzed. RESULTS: Over 1.5 years, the slope of BMD decline over time was slower at all quadrants for the active-resisted stance limbs. At >2 years of training, BMD was significantly higher for the active-resisted stance group than for the passive stance group (P = 0.007). BMD was preferentially spared in the posterior quadrants of the femur with active-resisted stance. CONCLUSIONS: A regional measurement technique revealed asymmetric femur BMD changes between passive stance and active-resisted stance. Future studies are now underway to better understand other regional changes in BMD after SCI.

Fatigue modulates synchronous but not asynchronous soleus activation during stimulation of paralyzed muscle.

OBJECTIVE: Electrical stimulation over a motor nerve yields muscle force via a combination of direct and reflex-mediated activation. We determined the influence of fatigue on reflex-mediated responses induced during supra-maximal electrical stimulation in humans with complete paralysis. METHODS: We analyzed soleus electromyographic (EMG) activity during repetitive stimulation (15 Hz, 125 contractions) in 22 individuals with complete paralysis. The bout of stimulation caused significant soleus muscle fatigue (53.1% torque decline). RESULTS: Before fatigue, EMG at all latencies after the M-wave was less than 1% of the maximal M-wave amplitude (% MaxM). After fatigue there was a fourfold (p < 0.05) increase in EMG at the H-reflex latency; however, the overall magnitude remained low (< 2% change in % MaxM). There was no increase in "asynchronous" EMG ∼ 1 s after the stimulus train. CONCLUSIONS: Fatigue enhanced the activation to the paralyzed soleus muscle, but primarily at the H-reflex latency. The overall influence of this reflex modulation was small. Soleus EMG was not elevated during fatigue at latencies consistent with asynchronous activation. SIGNIFICANCE: These findings support synchronous reflex responses increase while random asynchronous reflex activation does not change during repetitive supra-maximal stimulation, offering a clinical strategy to consistently dose stress to paralyzed tissues.

Doublet electrical stimulation enhances torque production in people with spinal cord injury.

BACKGROUND: Muscle fatigue prevents repetitive use of paralyzed muscle after spinal cord injury (SCI). OBJECTIVE: This study compared the effects of hybrid patterns of muscle stimulation in individuals with acute and chronic SCI. METHODS: Individuals with chronic (n = 11) or acute paralysis (n = 3) underwent soleus muscle activation with a constant (CT) or doublet (DT) stimulation train before and at various times after a fatigue protocol. RESULTS: The chronically paralyzed soleus was highly fatigable with a fatigue index (FI) of 19% ± 6%, whereas the acutely paralyzed soleus was fatigue resistant (FI = 89% ± 8%). For the chronically paralyzed group, the DT protocol caused less than 5% improvement in peak and mean force relative to the CT protocol before fatigue; however, after fatigue the DT protocol caused an increase in peak and mean force (>10%), compared with the CT protocol (P < .05). As the chronically paralyzed muscle developed low-frequency fatigue, the DT protocol became more effective than the CT protocol (P < .05). The DT protocol increased the rate of torque development before fatigue (42% ± 78%), after fatigue (62% ± 52%), and during recovery (87% ± 54% to 101% ± 56%; P < .05). The acutely paralyzed group showed minimal change in peak and mean torque with the DT protocol. CONCLUSIONS: Chronic reduced activity is associated with muscle adaptations (slow to fast) that render the muscle more amenable to force enhancement through doublet train activation after fatigue. These findings are applicable to patients using neuromuscular stimulation.

Enhancing muscle force and femur compressive loads via feedback-controlled stimulation of paralyzed quadriceps in humans.

OBJECTIVE: To compare paralyzed quadriceps force properties and femur compressive loads in an upright functional task during conventional constant-frequency stimulation and force feedback-modulated stimulation. DESIGN: Crossover trial. SETTING: Research laboratory. PARTICIPANTS: Subjects (N=13; 12 men, 1 woman) with motor-complete spinal cord injury. INTERVENTIONS: Subjects performed 2 bouts of 60 isometric quadriceps contractions while supported in a standing frame. On separate days, subjects received constant-frequency stimulation at 20Hz (CONST) or frequency-modulated stimulation triggered by a change in force (FDBCK). During FDBCK, a computer algorithm responded to each 10% reduction in force with a 20% increase in stimulation frequency. MAIN OUTCOME MEASURES: A biomechanical model was used to derive compressive loads on the femur, with a target starting dose of load equal to 1.5 times body weight. RESULTS: Peak quadriceps force and fatigue index were higher for FDBCK than CONST (P<.05). Within-train force decline was greater during FDBCK bouts, but mean force remained above CONST values (P<.05). As fatigue developed during repetitive stimulation, FDBCK was superior to CONST for maintenance of femur compressive loads (P<.05). CONCLUSIONS: Feedback-modulated stimulation in electrically activated stance is a viable method to maximize the physiologic performance of paralyzed quadriceps muscle. Compared with CONST, FDBCK yielded compressive loads that were closer to a targeted dose of stress with known osteogenic potential. Optimization of muscle force with FDBCK may be a useful tactic for future training-based antiosteoporosis protocols.

Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis.

In humans, spinal cord injury (SCI) induces deleterious changes in skeletal muscle that may be prevented or reversed by electrical stimulation muscle training. The molecular mechanisms underlying muscle stimulation training remain unknown. We studied two unique SCI subjects whose right soleus received >6 years of training (30 minutes/day, 5 days/week). Training preserved torque, fatigue index, contractile speed, and cross-sectional area in the trained leg, but not the untrained leg. Training decreased 10 mRNAs required for fast-twitch contractions and mRNA that encodes for myostatin, an autocrine/paracrine hormone that inhibits muscle growth. Conversely, training increased 69 mRNAs that mediate the slow-twitch, oxidative phenotype, including PGC-1α, a transcriptional coactivator that inhibits muscle atrophy. When we discontinued right soleus training, training-induced effects diminished slowly, with some persisting for >6 months. Training of paralyzed muscle induces localized and long-lasting changes in skeletal muscle mRNA expression that improve muscle mass and function.

Reliability and responsiveness of musculoskeletal ultrasound in subjects with and without spinal cord injury.

Rehabilitation after spinal cord injury (SCI) aims to preserve the integrity of the paralyzed musculoskeletal system. The suitability of ultrasound (US) for delineating training-related muscle/tendon adaptations after SCI is unknown. The purpose of this study was to quantify within- and between-operator reliability for US and to determine its responsiveness to post-training muscle/tendon adaptations in SCI subjects. Two novice operators and one experienced operator obtained sonographic images of the vastus lateralis, patellar tendon, soleus, and Achilles tendon from seven SCI subjects and 16 controls. For control subjects, within-operator concordance (ICC [3,1]) ranged from 0.58 to 0.95 for novice operators and exceeded 0.86 for the experienced operator. Between-operator concordance (ICC [2,1]) ranged from 0.62 to 0.74. Ultrasound detected muscle hypertrophy (p < 0.05) following electrical stimulation training in subjects with SCI (responsiveness) but did not detect differences in tendon thickness. These error estimates support the utility of US in future post-SCI training studies.

Repetitive eccentric muscle contractions increase torque unsteadiness in the human triceps brachii.

Torque steadiness and low-frequency fatigue (LFF) were examined in the human triceps brachii after concentric or eccentric fatigue protocols. Healthy young males (n=17) performed either concentric or eccentric elbow extensor contractions until the eccentric maximal voluntary torque decreased to 75% of pre-fatigue for both (concentric and eccentric) protocols. The number of concentric contractions was greater than the number of eccentric contractions needed to induce the same 25% decrease in eccentric MVC torque (52.2+/-2.9 vs. 41.5+/-2.1 for the concentric and eccentric protocols, respectively, p<.01). The extent of peripheral fatigue was approximately 12% greater after the concentric compared to the eccentric protocol (twitch amplitude), whereas LFF (increase in double pulse torque/single pulse torque), was similar across protocols. Steadiness, or the ability for a subject to hold a submaximal isometric contraction, was approximately 20 % more impaired during the Ecc protocol (p=.052). Similarly, the EMG activity required to hold the torque steady was nearly 20% greater after the eccentric compared to concentric protocol. These findings support that task dependent eccentric contractions preferentially alter CNS control during a precision based steadiness task.

Muscle and bone plasticity after spinal cord injury: review of adaptations to disuse and to electrical muscle stimulation.

The paralyzed musculoskeletal system retains a remarkable degree of plasticity after spinal cord injury (SCI). In response to reduced activity, muscle atrophies and shifts toward a fast-fatigable phenotype arising from numerous changes in histochemistry and metabolic enzymes. The loss of routine gravitational and muscular loads removes a critical stimulus for maintenance of bone mineral density (BMD), precipitating neurogenic osteoporosis in paralyzed limbs. The primary adaptations of bone to reduced use are demineralization of epiphyses and thinning of the diaphyseal cortical wall. Electrical stimulation of paralyzed muscle markedly reduces deleterious post-SCI adaptations. Recent studies demonstrate that physiological levels of electrically induced muscular loading hold promise for preventing post-SCI BMD decline. Rehabilitation specialists will be challenged to develop strategies to prevent or reverse musculoskeletal deterioration in anticipation of a future cure for SCI. Quantifying the precise dose of stress needed to efficiently induce a therapeutic effect on bone will be paramount to the advancement of rehabilitation strategies.

Dose estimation and surveillance of mechanical loading interventions for bone loss after spinal cord injury.

BACKGROUND AND PURPOSE: The interpretation of the results of previous anti-osteoporosis interventions after spinal cord injury (SCI) is undermined by incomplete information about the intervention dose or patient adherence to dose requirements. Rehabilitation research as a whole traditionally has struggled with these same issues. The purpose of this case report is to offer proof of the concepts that careful dose selection and surveillance of patient adherence should be integral components in rehabilitation interventions. CASE DESCRIPTION: A 21-year-old man with T4 complete paraplegia (7 weeks) enrolled in a unilateral soleus muscle electrical stimulation protocol. Compressive loads applied to the tibia approximated 1.4 times body weight. Over 4.8 years of home-based training, data logging software provided surveillance of adherence. Soleus muscle torque and fatigue index adaptations to training as well as bone mineral density (BMD) adaptations in the distal tibia were measured. OUTCOMES: The patient performed nearly 8,000 soleus muscle contractions per month, with occasional fluctuations. Adherence tracking permitted intervention when adherence fell below acceptable values. The soleus muscle torque and fatigue index increased rapidly in response to training. The BMD of the untrained tibia declined approximately 14% per year. The BMD of the trained tibia declined only approximately 7% per year. The BMD was preferentially preserved in the posterior half of the tibia; this region experienced only a 2.6% annual decline. DISCUSSION: Early administration of a load intervention, careful estimation of the loading dose, and detailed surveillance of patient adherence aided in the interpretation of a patient's adaptations to a mechanical load protocol. These concepts possess wider applicability to rehabilitation research and should be emphasized in future physical therapy investigations.

Musculoskeletal adaptations in chronic spinal cord injury: effects of long-term soleus electrical stimulation training.

OBJECTIVE: The purpose of this study was to determine whether long-term electrical stimulation training of the paralyzed soleus could change this muscle's physiological properties (torque, fatigue index, potentiation index, torque-time integral) and increase tibia bone mineral density. METHODS: Four men with chronic (>2 years) complete spinal cord injury (SCI; American Spinal Injury Association classification A) trained 1 soleus muscle using an isometric plantar flexion electrical stimulation protocol. The untrained limb served as a within-subject control. The protocol involved ~ 30 minutes of training each day, 5 days a week, for a period of 6 to 11 months. Mean compliance over 11 months of training was 91% for 3 subjects. A fourth subject achieved high compliance after only 5 months of training. Mean estimated compressive loads delivered to the tibia were approximately 110% of body weight. Over the 11 months of training, the muscle plantar flexion torque, fatigue index, potentiation index, and torque-time integral were evaluated periodically. Bone mineral density (dual-energy x-ray absorptiometry) was evaluated before and after the training program. RESULTS: The trained limb fatigue index, potentiation index, and torque-time integral showed rapid and robust training effects (P<.05). Soleus electrical stimulation training yielded no changes to the proximal tibia bone mineral density, as measured by dual-energy x-ray absorptiometry. The subject with low compliance experienced fatigue index and torque-time integral improvements only when his compliance surpassed 80%. In contrast, his potentiation index showed adaptations even when compliance was low. CONCLUSIONS: These findings highlight the persistent adaptive capabilities of chronically paralyzed muscle but suggest that preventing musculoskeletal adaptations after SCI may be more effective than reversing changes in the chronic condition.

Feedback-controlled stimulation enhances human paralyzed muscle performance.

Chronically paralyzed muscle requires extensive training before it can deliver a therapeutic dose of repetitive stress to the musculoskeletal system. Neuromuscular electrical stimulation, under feedback control, may subvert the effects of fatigue, yielding more rapid and extensive adaptations to training. The purposes of this investigation were to 1) compare the effectiveness of torque feedback-controlled (FDBCK) electrical stimulation with classic open-loop constant-frequency (CONST) stimulation, and 2) ascertain which of three stimulation strategies best maintains soleus torque during repetitive stimulation. When torque declined by 10%, the FDBCK protocol modulated the base stimulation frequency in three ways: by a fixed increase, by a paired pulse (doublet) at the beginning of the stimulation train, and by a fixed decrease. The stimulation strategy that most effectively restored torque continued for successive contractions. This process repeated each time torque declined by 10%. In fresh muscle, FDBCK stimulation offered minimal advantage in maintaining peak torque or mean torque over CONST stimulation. As long-duration fatigue developed in subsequent bouts, FDBCK stimulation became most effective ( approximately 40% higher final normalized torque than CONST). The high-frequency strategy was selected approximately 90% of the time, supporting that excitation-contraction coupling compromise and not neuromuscular transmission failure contributed to fatigue of paralyzed muscle. Ideal stimulation strategies may vary according to the site of fatigue; this stimulation approach offered the advantage of online modulation of stimulation strategies in response to fatigue conditions. Based on stress-adaptation principles, FDBCK-controlled stimulation may enhance training effects in chronically paralyzed muscle.

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training.

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potentiation characteristics of recently paralyzed soleus muscle. Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue potentiation during a repetitive soleus activation protocol that induced low-frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no torque potentiation in response to repetitive stimulation. Seven of these acute subjects completed 2 yr of home-based isometric soleus electrical stimulation training of one limb (compliance = 83%; 8,300 contractions/wk). With the early implementation of electrically stimulated training, potentiation characteristics of trained soleus muscles were preserved as in the acute postinjury state. In contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after spinal cord injury (SCI). A single acute SCI subject who was followed longitudinally developed potentiation characteristics very similar to the untrained limbs of the training subjects. The results of the present investigation support that postfatigue potentiation is a characteristic of fast-fatigable muscle and can be prevented by timely neuromuscular electrical stimulation training. Potentiation is an important consideration in the design of functional electrical stimulation control systems for people with SCI.

Electrically induced muscle contractions influence bone density decline after spinal cord injury.

STUDY DESIGN: Longitudinal repeated-measures; within-subject control. OBJECTIVE: We examined the extent to which an isometric plantar flexion training protocol attenuates bone loss longitudinally after SCI. SUMMARY OF BACKGROUND DATA: After spinal cord injury (SCI), bone mineral density (BMD) of paralyzed extremities rapidly declines, likely because of loss of mechanical loading of bone via muscle contractions. METHODS: Six individuals with complete paralysis began a 3-year unilateral plantar flexor muscle activation program within 4.5 months after SCI. The opposite limb served as a control. Compliance with recommended dose was > 80%. Tibia compressive force was > 140% of body weight. RESULTS: Bilateral hip and untrained tibia BMD declined significantly over the course of the training. Lumbar spine BMD showed minimal change. Percent decline in BMD (from the baseline condition) for the trained tibia (approximately 10%) was significantly less than the untrained tibia (approximately 25%) (P < 0.05). Trained limb percent decline in BMD remained steady over the first 1.5 years of the study (P < 0.05). CONCLUSIONS: Compressive loads of approximately 1 to 2 times body weight, induced by muscle contractions, partially prevent the loss of BMD after SCI. Future studies should establish dose-response curves for attenuation of bone loss after SCI.