Locomotor Training Research Articles

Taking the Next Step in Neurologic Rehabilitation: Contributions of Intensity and Variability of Stepping Tasks during Locomotor Training.

Research over the past 20years indicates the amount of task-specific walking practice provided to individuals with stroke, brain injury, or incomplete spinal cord injury can strongly influence walking recovery. However, more recent data suggest that attention towards 2 other training parameters, including the intensity and variability of walking practice, may maximize walking recovery and facilitate gains in non-walking outcomes. The combination of these training parameters represents a stark contrast from traditional strategies, and confusion regarding the potential benefits and perceived risks may limit their implementation in clinical practice. The purpose of this perspective is to delineate the evidence regarding the contributions of intensity and variability of locomotor training to improve mobility outcomes in individuals with acute-onset brain and spinal cord injury. The rationale and evidence supporting the utility of these training parameters in controlled laboratory settings is first described by integrating concepts in the field of neuroscience, motor learning, biomechanics, and exercise physiology into a rehabilitation intervention. Subsequently, the evidence supporting the efficacy of this paradigm is addressed, including discussions of some of the misconceptions regarding perceived negative consequences of these strategies in an effort to mitigate common clinical concerns. Finally, the utility of these strategies implemented during inpatient rehabilitation is delineated to facilitate a more comprehensive understanding of the feasibility and potential benefits early following neurologic injury. A greater understanding of how and why to integrate higher intensity, variable stepping practice will support therapists to take the next step to maximize mobility in the patients they serve.

Spinal cord epidural stimulation for male sexual function in spinal cord injured rats.

95% of men with spinal cord injuries exhibit difficulties with sexual function, including erectile dysfunction, anejaculation, retrograde ejaculation, poor ejaculatory force, and poor sperm quality. The primary goal is to determine if well-established interventions, such as spinal cord epidural stimulation, are a feasible treatment for sexual dysfunction and if locomotor recovery training can be used to improve ejaculatory function in a rodent model of spinal cord injury (SCI). Male Wistar rats underwent thoracic laminectomies (shams), spinal cord transections, or moderate spinal cord contusion injuries. In urethane-anesthetized rodents, terminal spinal cord epidural stimulation was performed to target the mid-lumbar level spinal generator for ejaculation (SGE) in animals with transection spinal cord injuries at 3-, 14-, or 70-days post-injury and in animals with sham surgeries and spinal cord contusions at 70days post-injury. The impact of locomotor training frequency was examined in two groups of rats with spinal cord contusion, which underwent 1-hr of assisted plantar stepping on a treadmill, training two or five times weekly for 6weeks. Terminal experiments in all groups were followed by measures of sperm concentration and post-mortem testicular weight and morphology. Spinal cord epidural stimulation consistently induced the expulsion phase of ejaculation, and occasionally the emission phase of ejaculation in rats with chronic SCI. All animals were most responsive to spinal cord epidural stimulation combined with manual stimulation to induce ejaculation, with chronic injury resulting in the most consistent responses. Locomotor training improved response rates to spinal cord epidural stimulation, with intermittent training resulting in the most consistent induction of both the emission and expulsion phases of ejaculation. Sperm concentration was impacted by injury completeness and time-post injury, which was lowest in the chronic complete transection group of rats. Locomotor training resulted in an overall increase in sperm concentration, with 2days per week of training resulting in a significant improvement of sperm motility. Spinal cord epidural stimulation combined with locomotor training is a feasible intervention for individuals with SCI who seek to regain sexual function. Although we have anecdotal reports of non-targeted L3 spinal cord epidural stimulation inducing ejaculation in humans having spinal cord injuries, the current outcomes may be underestimated as stimulation was carried out in anesthetized animals. Spinal cord epidural stimulation to target the SGE is a feasible intervention for sexual dysfunction following SCI.

A research protocol to study the critical time window for rehabilitation after incomplete spinal cord injury: early vs. late locomotor training

Spinal cord injury (SCI) often results in severe motor and sensory deficits, leading to significant disability. Preclinical studies and retrospective studies suggest that a critical window of enhanced neuroplasticity may exist immediately after SCI, during which therapeutic interventions could yield greater functional improvements. The impact of time interval since SCI on efficacy of rehabilitation has not been directly assessed and is the focus of this clinical trial. This study will compare the efficacy of high-intensity gait training, initiated at different time intervals post-injury, on walking performance in individuals with SCI. We hypothesize that early intervention will yield the greatest improvements in walking ability and community ambulation, compared to training initiated at 3 or 6 months after SCI, or standard of care. This randomized, multi-site clinical trial will enroll 108 participants with acute, traumatic SCI. Participants will be randomized to receive 20 h of high-intensity gait training that will be initiated either early (< 60 days post-SCI), sub-acute (3 months), chronic (6 months), or to a control group receiving standard of care. Primary outcomes include gait speed (10 m Walk Test) and walking endurance (6-Minute Walk Test). Secondary outcomes include daily step count via wearable sensors, lower extremity strength, and quality of life measures. Assessments will occur at baseline, pre/post-intervention, and at 3, 6, 9, and 12 months post-SCI. This study will provide insights into the optimal timing of rehabilitation post-SCI and could have profound effects on our approach to training individuals with SCI in the healthcare setting as well as long term recovery outcomes.Trial registration ClinicalTrials.gov NCT06176833 was completed on 12/11/2023.

The Effect of Locomotor Training on Gait Parameters in Pediatric Patients with Cerebral Palsy: a Systematic Review and Meta-analysis

Background. Locomotor training is a relatively new approach in pediatric cerebral palsy, so there is still a lack of data on its effect of such training on walking function. Aim. To evaluate the effect of locomotor training on gait parameters in pediatric patients with cerebral palsy by reviewing the scientific literature. Methods. A systematic review with meta-analysis was conducted based on the results of the PubMed (MEDLINE) and the CINAHL Ultimate (EBSCOhost) searches for randomized clinical trials. Results. Fifteen eligible randomized clinical trials involving 375 pediatric patients with cerebral palsy were included. The results of the meta-analysis showed that locomotor training interventions, compared to standard treatment methods for cerebral palsy, have a small effect on walking speed (Cohen d = 0,16), cadence (Cohen d = 0,16) and step length (Cohen d = 0,18). Conclusions. There is evidence that supplementing standard treatment with locomotor training interventions has a small positive and lasting effect on walking speed, cadence and step length in pediatric patients with cerebral palsy. Keywords: cerebral palsy, children, locomotor training, spatiotemporal gait parameters.

An open-label, randomized, controlled trial on the benefit of β-hydroxy-β-methyl butyrate, l-arginine, l-glutamine combination beverages and locomotion training as supportive care for the treatment of unresectable hepatocellular carcinoma using lenvatinib: A pilot study (HELLO study).

Hand-foot-skin reaction (HFSR) is the most common side effect of multi-tyrosine kinase inhibitor therapy for unresectable hepatocellular carcinoma (uHCC). Sarcopenia has been reported to be a poor prognostic factor for HCC. Here, we performed a randomized controlled trial (RCT) of the efficacy of a β-hydroxy-β-methyl butyrate/L-arginine/L-glutamine (HMB/Arg/Gln) beverage and locomotion training as supportive care in the treatment of uHCC with lenvatinib. A total of 20 patients were enrolled from the jRCTs031190252 trial in this pilot study. HFSR was the primary endpoint, and other adverse events and skeletal muscle index at the third lumbar level (L3-SMI) were secondary endpoints. Twelve patients had albumin-bilirubin grade 1, and eight had grade 2. No difference in HFSR was observed. Although interesting differences were observed in the secondary endpoints, a slight retention of L3-SMI values in the intervention group compared with that in the control group was observed(96.5% vs. 89.9%, p=0.407). Although the HMB/Arg/Gln beverage and locomotion training did not reduce adverse events caused by lenvatinib, they might be useful in maintaining skeletal muscle mass. Further validation studies with a larger number of patients are warranted.

On the role of visual feedback and physiotherapist-patient interaction in robot-assisted gait training: an eye-tracking and HD-EEG study

BackgroundTreadmill based Robotic-Assisted Gait Training (t-RAGT) provides for automated locomotor training to help the patient achieve a physiological gait pattern, reducing the physical effort required by therapist. By introducing the robot as a third agent to the traditional one-to-one physiotherapist-patient (Pht-Pt) relationship, the therapist might not be fully aware of the patient’s motor performance. This gap has been bridged by the integration in rehabilitation robots of a visual FeedBack (FB) that informs about patient’s performance. Despite the recognized importance of FB in t-RAGT, the optimal role of the therapist in the complex patient-robot interaction is still unclear. This study aimed to describe whether the type of FB combined with different modalities of Pht’s interaction toward Pt would affect the patients’ visual attention and emotional engagement during t-RAGT.MethodsTen individuals with incomplete Spinal Cord Injury (C or D ASIA Impairment Scale level) were assessed using eye-tracking (ET) and high-density EEG during seven t-RAGT sessions with Lokomat where (i) three types of visual FB (chart, emoticon and game) and (ii) three levels of Pht-Pt interaction (low, medium and high) were randomly combined. ET metrics (fixations and saccades) were extracted for each of the three defined areas of interest (AoI) (monitor, Pht and surrounding) and compared among the different experimental conditions (FB, Pht-Pt interaction level). The EEG spectral activations in theta and alpha bands were reconstructed for each FB type applying Welch periodogram to data localised in the whole grey matter volume using sLORETA.ResultsWe found an effect of FB type factor on all the ET metrics computed in the three AoIs while the factor Pht-Pt interaction level also combined with FB type showed an effect only on the ET metrics calculated in Pht and surrounding AoIs. Neural activation in brain regions crucial for social cognition resulted for high Pht-Pt interaction level, while activation of the insula was found during low interaction, independently on the FB used.ConclusionsThe type of FB and the way in which Pht supports the patients both have a strong impact on patients’ engagement and should be considered in the design of a t-RAGT-based rehabilitation session.

EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) ASSOCIATED WITH BALANCE TRAINING IN INDIVIDUALS WITH PARKINSON'S: STUDY PROTOCOL FOR A RANDOMIZED CLINICAL TRIAL

The present study aimed to investigate the effects of balance training associated with cerebellar tDCS on postural control in individuals with PD. This is a randomized clinical trial in which individuals were allocated to an experimental group (EG) or placebo group (PG), in which a conventional protocol of 10 Physiotherapy sessions for locomotor training and postural control was applied. In the EG, tDCS was applied, with a current setting of 1.5 mA for 20 minutes simultaneously with postural control training. In the PG, tDCS was applied in sham mode, with the same electrode positioning and the same number of sessions as the EG. The sample compared 34 individuals with PD (EG: 17; PG: 17).Cerebellar tDCS associated with balance training may help improve postural control and balance in walkers with Parkinson's Disease. The hypothesis is, if walking improve, the benefits may be accompanied by better balance and reduced fear of falling, and individuals may experience greater free-living physical activity at home and in the community.

Activity-based locomotor training: improving the movement in children with spinal cord injury

Activity-based locomotor training: improving the movement in children with spinal cord injury

A retrospective analysis of a clinician-initiated high-intensity locomotor training implementation project in an inpatient rehabilitation facility.

The Academy of Neurologic Physical Therapy's Intensity Matters campaign recommends the implementation of high-intensity locomotor training for all patients with neurologic dysfunction with goals to improve walking. Retrospectively determine the effectiveness of a clinician-initiated implementation project on the adoption, reach, and fidelity of high-intensity locomotor training for patients with stroke during inpatient rehabilitation and, determine whether the project led to changes in patient outcomes. Retrospective analysis of electronic medical records from 1 year before and after the project. Patients admitted with a stroke diagnosis were included. Demographic information, the number of high-intensity sessions, the percentage of time spent in the target heart rate zone, standardized assessment scores for motor function, functional mobility, balance, gait speed and endurance, and discharge destination were extracted for descriptive and linear mixed model analysis. Clinician reach was 75%, and adoption of high-intensity training varied between clinicians from 47.1% and 83.3%. Of eligible patients, 55% received the target intervention at least once, reflecting the patient reach. Implementation fidelity was 18.84%. Linear mixed effects modeling revealed a statistically significant effect of time (p < .001) but not group allocation or group × time interaction. Although statistically significant differences in patient outcomes compared to pre-implementation were not found, results highlight the limitations associated with adopting high-intensity locomotor training for patients post-stroke in this setting .It remains unclear whether the implementation fidelity achieved was sufficient to impact patient outcomes. Further research is needed to establish fidelity targets and identify barriers to successful implementation projects by clinicians.

An Exploration of Locomotor Syndrome among Geriatric Population – A Narrative Review

A locomotor disability in the geriatric population is a physical condition that impairs mobility and movement in older persons. It is frequently caused by age-related causes such as degenerative diseases, osteoarthritis, or neurological abnormalities. This impairment can have a substantial influence on older people's quality of life by limiting their ability to conduct daily activities independently, such as walking, standing, or climbing stairs. Addressing locomotor impairments in older persons is critical for preserving their mobility, independence, and overall well-being, ultimately improving their quality of life as they age.A comprehensive literature search was conducted, which were sourced from PubMed, google scholar, Japanese government websites, springer link, semantic scholar generated significant studies using the keywords like locomotor disability, older population, mobility, quality of life, aging. We included articles which were published from 2005–2024.Locomotive Syndrome (LS) affects a significant portion of the elderly population, with prevalence ranging from 8.4% to 50.3%, increasing with age and higher in women. It shows the correlations with osteoporosis and sarcopenia, suggesting potential shared risk factors or pathways. By this the older people tend to have lower quality of life, particularly concerning spinal alignment and trunk deformity. Exercise interventions, including locomotive training, aerobic exercise, and muscle training, are suggested for LS prevention. Vitamin D supplementation may benefit bone health and fall prevention in older individuals.Locomotor syndrome is a substantial concern, especially in ageing populations, with considerable implications for quality of life. Its prevalence, which is frequently associated with osteoporosis and sarcopenia, highlights the necessity of preventive measures including exercise and vitamin D supplementation. Recognising the impact of LS on mobility and well-being is critical for establishing focused interventions to prevent and manage its progression, thereby improving the overall health and independence of geriatric population.

Critically appraised paper: High-intensity interval training results in greater walking capacity at 8 and 12 weeks than moderate-intensity locomotor training in chronic stroke

Critically appraised paper: High-intensity interval training results in greater walking capacity at 8 and 12 weeks than moderate-intensity locomotor training in chronic stroke

Predicting Walking Capacity Outcomes After Moderate to High Intensity Locomotor Training in Chronic Stroke.

Moderate-to-high intensity locomotor training (M-HIT) is strongly recommended in stroke rehabilitation but outcomes are variable. This study aimed to identify baseline clinical characteristics that predict change in walking capacity following M-HIT in chronic stroke. This analysis used data from the HIT-Stroke Trial (N=55), which involved up to 36 sessions of either moderate or high intensity locomotor training. A prespecified model assessed how well baseline motor impairment (Fugl-Meyer lower limb motor scale [FM-LL]), comfortable gait speed (CGS), and balance confidence (Activities Balance Confidence scale [ABC]), independently explain changes in 6-minute walk distance (Δ6MWD), while controlling for treatment group. Exploratory analysis tested additional baseline covariates using the all-possible regressions procedure. The prognostic value of each potential covariate was assessed by its average contribution to the explained variance in Δ6MWD (Δ pseudo-R 2 ). With the prespecified model, 8-week Δ6MWD was significantly associated with baseline FM-LL (β=5.0 [95% CI: 1.4, 8.6]) and ABC (β=0.7 [0.0, 1.4]), but not CGS (β=-44.6 [-104.7, 15.6]). The exploratory analysis revealed the top 7 covariates with the highest mean Δ pseudo-R 2 were: FM-LL, pain-limited walking duration, ABC, the use of an assistive device, fatigue, depression, and recent walking exercise history >2 days per week. On average, participants with less motor impairment and higher balance confidence have greater walking capacity improvements after M-HIT in chronic stroke. Additional negative prognostic factors may include pain-limited walking duration, use of an assistive device, fatigue, depression, and recent walking exercise but these exploratory findings need to be confirmed in future studies.

Amplify Gait to Improve Locomotor Engagement in Spinal Cord Injury (AGILE SCI) trial: study protocol for an assessor blinded randomized controlled trial

BackgroundAmong ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.g., error augmentation) can accelerate motor learning by intensifying sensorimotor feedback and facilitating exploration of motor control strategies. These features may be beneficial for retraining walking balance after iSCI. We have developed a cable-driven robot that creates a movement amplification environment during treadmill walking. The robot applies a continuous, laterally-directed, force to the pelvis that is proportional in magnitude to real-time lateral velocity. Our purpose is to investigate the effects of locomotor training in this movement amplification environment on walking balance. We hypothesize that for ambulatory people with iSCI, locomotor training in a movement amplification environment will be more effective for improving walking balance and participation in walking activities than locomotor training in a natural environment (no applied external forces).MethodsWe are conducting a two-arm parallel-assignment intervention. We will enroll 36 ambulatory participants with chronic iSCI. Participants will be randomized into either a control or experimental group. Each group will receive 20 locomotor training sessions. Training will be performed in either a traditional treadmill environment (control) or in a movement amplification environment (experimental). We will assess changes using measures that span the International Classification of Functioning, Disability and Health (ICF) framework including 1) clinical outcome measures of gait, balance, and quality of life, 2) biomechanical assessments of walking balance, and 3) participation in walking activities quantified by number of steps taken per day.DiscussionTraining walking balance in people with iSCI by amplifying the individual’s own movement during walking is a radical departure from current practice and may result in new strategies for addressing balance impairments. Knowledge gained from this study will expand our understanding of how people with iSCI improve walking balance and how an intervention targeting walking balance affects participation in walking activities. Successful outcomes could motivate development of clinically feasible tools to replicate the movement amplification environment within clinical settings.Trial registrationNCT04340063.

Sleep benefits perceptual but not movement-based learning of locomotor sequences

Practicing complex locomotor skills, such as those involving a step sequence engages distinct perceptual and motor mechanisms that support the recall of learning under new conditions (i.e., skill transfer). While sleep has been shown to enhance learning of sequences of fine movements (i.e., sleep-dependent consolidation), here we examined whether this benefit extends to learning of a locomotor pattern. Specifically, we tested the perceptual and motor learning of a locomotor sequence following sleep compared to wake. We hypothesized that post-practice sleep would increase locomotor sequence learning in the perceptual, but not in the motor domain. In this study, healthy young adult participants (n = 48; 18–33 years) practiced a step length sequence on a treadmill cued by visual stimuli displayed on a screen during training. Participants were then tested in a perceptual condition (backward walking with the same visual stimuli), or a motor condition (forward walking but with an inverted screen). Skill was assessed immediately, and again after a 12-h delay following overnight sleep or daytime wake (n = 12 for each interval/condition). Off-line learning improved following sleep compared to wake, but only for the perceptual condition. Our results suggest that perceptual and motor sequence learning are processed separately after locomotor training, and further points to a benefit of sleep that is rooted in the perceptual as opposed to the motor aspects of motor learning.

The combined effect of leucine-enriched essential amino acid supplements and locomotion training on physical functions and quality of life in hemodialysis patients

BackgroundLocomotive syndrome (LS) is a condition of reduced mobility (locomotive organ impairment) that is associated with reduced quality of life (QOL) in patients undergoing hemodialysis (HD), and effective interventions for patients with LS undergoing HD are unclear. We conducted a clinical trial to assess the effects of exercise and oral nutritional supplementation (ONS) on QOL in this cohort.MethodsThis study was an open-label, randomized controlled trial. The participants were patients with LS undergoing HD. The intervention period was 3 months. The primary outcome was a change in the physical component summary (PCS) of QOL, and the secondary outcomes were changes in other QOL scores, physical function, body composition, and nutritional status assessed by using the geriatric nutritional risk index. Participants were divided into the locomotion training (LT) and LT + ONS groups. Both groups were instructed on LT that comprised one-leg standing and squats to be carried out four or more times per week. The ONS consisted of 3 g leucin-rich essential amino acids and 800 IU vitamin D per pack, and the participants in the LT + ONS group received one pack of the supplement per day.ResultsIn total, 40 individuals undergoing HD were included in the study; 3 patients in the LT + ONS group were excluded from the analysis because of hospitalization and incomplete assessment. The median age was 73 years (interquartile range: 62–80 years), 23 participants were men (62%), and the duration of dialysis treatment was 6 years (interquartile range: 3–16 years). The change in PCS of the LT + ONS group did not differ from that in the LT group [LT + ONS: −1.6 (−5.3, 6.8) versus LT: −0.1 (−5.3, 6.2), p = 0.94]. In contrast, the LT + ONS group showed maintenance in mental health (MH) and improvement of the two-step value.ConclusionsThe LT + ONS group did not show an effect on PCS in QOL compared with only LT in patients with LS undergoing HD. However, maintenance of MH and improvement of two-step value were confirmed in the LT + ONS group. Future research is need to confirm whether leucine-rich essential amino acids and vitamin D help mental health and physical function in patients with LS undergoing HD with larger sample sizes and long-term interventions.Clinical trial registration University Hospital Medical Information Network Center (UMIN 000032457).

Exercise role on inflammatory and MCH-1 plasticity markers in severely contused spinal cord injured rodents

Approximately 17,500 new cases of Spinal cord Injury (SCI) occur annually in the United States. Growing evidence suggests that mobilizing the body following SCI through physical therapy regimens can help patients regain locomotor function. The immune response and the role of inflammation following SCI represents an important factor contributing to plasticity and recovery of function post-injury. The immune response uses both pro and anti-inflammatory factors to facilitate healing at the primary and secondary injury. In the severe case of SCI, inflammation can lead to maladaptive plasticity and that can hinder locomotor recovery. Pro-inflammatory cytokines such as Tumor necrosis factor alpha (TNF-a) can enhance the C-fiber activation in the dorsal horn resulting in sensitization and maladaptive plasticity. Exercise can also be pro-inflammatory. Exercise has been shown to decrease TNF-a levels and increases Interleukin-10 (IL-10) in human skeletal muscle. Bodyweight treadmill training in SCI animal has shown improvements in locomotor function. Interleukin-10 (IL-10), demonstrates potent anti-inflammatory effects in which it down-regulates TNF-alpha and its secondary effects. In addition, major histocompatibility complex class I proteins (MHC1), play a vital role in maintaining the structural integrity of neurons which is critical for fostering an environment for spinal plasticity to occur. In this study, we focus on the role of training paradigms to be used to facilitate locomotor recovery in spinally contused rats. The Body-Weight Supported Treadmill Training (BWSTT) and circular Bodyweight-Supported Ambulatory Rodent Trainer (cBART) both represent locomotor training for SCI animals. Mid-thoracic spinal cord contusion was performed, and the animals were allowed to recover for two weeks. The contused BWSTT alone, or cBART alone or combined BWSTT and cBART training groups were initiated at beginning of the third week for a total of 8-weeks of training. Controls include contused rats that received no training, and intact group (SHAM). At 10 weeks, the spinal cord was dissected for qPCR study. We measure the levels of TNF-alpha, MHC1, and IL-10 in the thoracic segment above the injury site, the injury site, Lumbar 1-3 and Lumbar 3-5 segment. Results show that in the cBART trained group, the MHC-1 expression in the L3-L5 segment was significantly greater when compared to the contused injury with no training intervention. No training effect was realized in MHC-1 in the L1-L3 trained groups. The training paradigms did not modulate TNF-a levels in the lumbar spinal cord segments. Lastly, IL-10 expression was undetectable in all the spinal cord segments. In this severe spinal cord contused model, we were only able to show modulation in the MHC-1 expression in the trained lumbar segment as function of exercise. Additional work will be required to consider the intensity of locomotor training and the severity of spinal cord contusion impact on these plasticity markers. Future understanding of these mechanisms may be useful in developing better locomotor training methods and drug targets for facilitation of recovery following SCI. CSULA RSCA 2020 MINI Grant- Dr. Joseph CSULA MORE Programs Offce, MBRS-URISE (1734GM145503) Bridges to Doctorate 5T23GM146700 NIH R25HD097701-04 - Dr. Ray De Leon. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of Walking Adaptability Training on Walking Capacity in Ambulatory People With Motor Incomplete Spinal Cord Injury: A Multicenter Pragmatic Randomized Controlled Trial

Background and Objective Balance and walking capacity are often impaired in people with motor incomplete spinal cord injury (iSCI), frequently resulting in reduced functional ambulation and participation. This study aimed to assess the efficacy of walking adaptability training compared to similarly dosed conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, and participation in ambulatory people with iSCI. Methods We conducted a 2-center, parallel-group, pragmatic randomized controlled trial. Forty-one people with iSCI were randomized to 6 weeks of (i) walking adaptability training (11 hours of Gait Real-time Analysis Interactive Lab (GRAIL) training—a treadmill in a virtual reality environment) or (ii) conventional locomotor and strength training (11 hours of treadmill training and lower-body strength exercises). The primary measure of walking capacity was maximal walking speed, measured with an overground 2-minute walk test. Secondary outcome measures included the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP), the Activities-specific Balance Confidence (ABC) scale, and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). Results No significant difference in maximal walking speed between the walking adaptability (n = 17) and conventional locomotor and strength (n = 18) training groups was found 6 weeks after training at follow-up (−0.05 m/s; 95% CI = −0.12-0.03). In addition, no significant group differences in secondary outcomes were found. However, independent of intervention, significant improvements over time were found for maximal walking speed, SCI-FAP, ABC, and USER-P restrictions scores. Conclusions. Our findings suggest that walking adaptability training may not be superior to conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, or participation in ambulatory people with iSCI. Trial Registration Dutch Trial Register; Effect of GRAIL training in iSCI.

Effects of γ-aminobutyric acid (GABA) intake in combination with exercise on muscle strength in humans with decreased mobility: a randomized, double-blind, placebo-controlled, parallel-group study

Background: Aging-related declines in skeletal muscle mass, muscle strength, and physical function are related to instability, falls, and frailty in older people, resulting in the need for nursing care. Objective: To investigate the effect of oral γ-aminobutyric acid (GABA) intake and exercise on muscle parameters in healthy subjects whose muscle strength is beginning to decline with age. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted. Fifty subjects (over 40 years old) were randomly divided into the GABA (100 mg/day) or placebo food intake group. Subjects orally consumed the respective study substance every day for 12 weeks. They performed daily “locomotion training” as devised by the Japanese Orthopedic Society. Muscle mass, fat mass, and knee extension muscle strength were measured. Results: The two groups had no significant differences in muscle and fat mass. Compared with the placebo food group, the GABA group showed a significant improvement in knee extension muscle strength in the left and right legs at pre-dose Week 0 (at Week 6, p = 0.02). In post hoc subgroup analysis by sex, when compared with the placebo food intake group, the GABA food intake group showed significant improvement in knee extension muscle strength of the right leg at Weeks 6 (p = 0.001) and 12 (p = 0.007), the left leg at Week 6 (p = 0.02), the stronger of the left and right legs at pre-dose Week 0 (at Week 6, p = 0.001), and the weaker of the left and right legs at pre-dose Week 0 (at Week 12, p = 0.013) in males. Conclusions: These results suggest that GABA intake combined with daily exercise is effective for maintaining knee extension muscle strength, which decreases with age. Furthermore, there were no safety issues with the intake of GABA-containing food during this study. Trial registration: UMIN-CTR: UMIN000050152. Keywords: γ-Aminobutyric acid, GABA, Muscle mass, Knee extension muscle strength, Aging

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Exploring How the Arms Can Help the Legs in Facilitating Gait Rehabilitation.

Inspired by the ideas from the fields of gait rehabilitation, neuroscience, and locomotion biomechanics and energetics, a body of work is reviewed that has led to propose a conceptual framework for novel "self-assistive" walking devices that could further promote walking recovery from incomplete spinal cord injuries. The underlying rationale is based on a neural coupling mechanism that governs the coordinated movements of the arms and legs during walking, and that the excitability of these neural pathways can be exploited by actively engaging the arms during locomotor training. Self-assistive treadmill walking rehabilitation devices are envisioned as an approach that would allow an individual to actively use their arms to help the legs during walking. It is hoped that the conceptual framework inspires the design and use of self-assistive walking devices that are tailored to assist individuals with an incomplete spinal cord injury to regain their functional walking ability.