LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction.

LMNA-related muscular dystrophy is an autosomal-dominant progressive disorder caused by mutations in LMNA. LMNA missense mutations are becoming correctable with CRISPR/Cas9-derived tools. Evaluating the functional recovery of LMNA after gene editing bears challenges as there is no reported direct loss of function of lamin A/C proteins in patient-derived cells. The proteins encoded by LMNA are lamins A/C, important ubiquitous nuclear envelope proteins but absent in pluripotent stem cells. We induced lamin A/C expression in induced pluripotent stem cells (iPSCs) of two patients with LMNA-related muscular dystrophy, NM_170707.4 (LMNA): c.1366A > G, p.(Asn456Asp) and c.1494G > T, p.(Trp498Cys), using a short three-day, serum-induced differentiation protocol and analyzed expression profiles of co-regulated genes, examples being COL1A2 and S100A6. We then performed precise gene editing of LMNA c.1366A > G using the near-PAMless (PAM: protospacer-adjacent motif) cytosine base editor. We show that the mutation can be repaired to 100% efficiency in individual iPSC clones. The fast differentiation protocol provided a functional readout and demonstrated increased lamin A/C expression as well as normalized expression of co-regulated genes. Collectively, our findings demonstrate the power of CRISPR/Cas9-mediated gene correction and effective outcome measures in a disease with, so far, little perspective on therapies.

No beneficial effect of aerobic whole-body electromyostimulation on lower limbs strength and power - a randomized controlled trial.

BACKGROUND: Applying whole-body electromyostimulation (wbEMS) to voluntary activation of the muscle is known to impact motor unit recruitment. Thus, wbEMS as an additional training stimulus enhances force-related capacities. This study aimed to evaluate the mono- and multiarticular strength adaptations to a running intervention with wbEMS compared to running without wbEMS. METHODS: In a randomized controlled trial (RCT), 59 healthy participants (32 female/ 27 male, 41 ± 7 years) with minor running experience conducted an eight-week running intervention (2x/ week à 20 min) with a wbEMS suit (EG) or without wbEMS (control group, CG). Maximal isokinetic knee extensor and flexor strength and jump height during countermovement jumps were recorded prior and after the intervention to assess maximal strength and power. RESULTS: Following eight weeks of running, maximal isokinetic knee extension torque decreased significantly over time for both interventions (EG Δ -4%, CG Δ -4%; F(1, 44.14) = 5.96, p = 0.02, η = 0.12). No changes were observed for flexion torque (F(1, 43.20) = 3.93, p = 0.05, η = 0.08) or jump height (F(1, 43.04) = 0.32, p = 0.57, η  = 0.01). CONCLUSIONS: The outcomes indicate that there is no additional effect over neuromuscular function adaptations with the inclusion of wbEMS during running training. Knee extensor strength is even slightly reduced which supports the principle of training specificity in regards to strength adaptation. We conclude that strength improvements cannot be achieved by running with wbEMS. TRIAL REGISTRATION: German Clinical Trials Register, ID DRKS00026827, date 10/26/21.

Whole-Body Electromyostimulation Impacts Physiological Responses During Aerobic Running: A Randomized Trial.

Objective: The aim of the current study was to evaluate the physiological and metabolic responses to running with whole-body electromyostimulation (wbEMS) compared to running without electromyostimulation (control, CG). Methods: Twenty healthy participants (9 male/11 female, age 42 ±7 years) conducted an incremental step test with respiratory gas analysis until exhaustion. Trials were conducted as wbEMS and CG in a random order. As outcome measures, (A) objective total exhaustion, (B) athletic responses (max. time and velocity) and (C) physiological and metabolic responses (V'O2/ kg, V'E, EE, RER, lactate) were compared. (D) The impact on the skeletal muscle was assessed prior, 48 h & 72 h after trial. Results: During both trials, participants (A) ran until total exhaustion. Nonetheless, (B) time and velocity till exhaustion as well as (C) RER prior to the first lactate threshold and V'E were reduced with wbEMS. All other correlates did not differ significantly between wbEMS and CG. Following 48 h and 72 h after the trial with wbEMS, (D) the impact on the skeletal muscle was 7- to 9-fold higher compared to baseline values. Values differed significantly to those after running without wbEMS. Conclusion: With the additional stimulation during voluntary activation, wbEMS induces earlier fatigue and a shift in energy metabolism toward fat utilization. Even during aerobic endurance tasks, a great impact on the skeletal muscle indicated by the rise in CK could be observed which promotes wbEMS as an alternative training stimulus that is easy-to-apply and effective during endurance training.

Running with whole-body electromyostimulation improves physiological determinants of endurance performance - a randomized control trial.

BACKGROUND: This study aimed to evaluate the physiological and metabolic adaptations to an eight-week running intervention with whole-body electromyostimulation (wbEMS) compared to running without wbEMS. METHODS: In a randomized controlled trial (RCT), 59 healthy participants (32 female/ 27 male, 41 ± 7 years, rel.V̇O2max 40.2 ± 7.4 ml/min/kg) ran twice weekly à 20 min for eight weeks either with a wbEMS suit (EG) or without wbEMS (control group, CG). Before and after the intervention, (i) rel.V̇O2max, heart rate and time to exhaustion were recorded with an incremental step test with an incremental rate of 1.20 km/h every 3 min. They were interpreted at aerobic and (indirect) anaerobic lactate thresholds as well as at maximum performance. (ii) Resting metabolic rate (RQ) as well as (iii) body composition (%fat) were assessed. RESULTS: Following the intervention, V̇O2max was significantly enhanced for both groups (EG ∆13 ± 3%, CG ∆9 ± 3%). Velocity was elevated at lactate thresholds and maximum running speed (EG ∆3 ± 1%, CG ∆2 ± 1%); HRmax was slightly reduced by -1 beat/min. No significant changes were observed for time until exhaustion and lactate. RQ was significantly enhanced following both trainings by + 7%. %fat was reduced for both groups (EG ∆-11 ± 3%, CG ∆-16 ± 5%), without any changes in body mass. Results did not differ significantly between groups. CONCLUSIONS: Both interventions had a positive impact on aerobic power. The rightward shift of the time-velocity graph points towards improved endurance performance. The effects of wbEMS are comparable to those after high-intensity training and might offer a time-efficient alternative to affect physiological and metabolic effects. TRIAL REGISTRATION: German Clinical Trials Register, ID DRKS00026827, date 10/26/21.

Effects of electromyostimulation on physiological determinants of endurance-performance in healthy subjects: a systematic review.

INTRODUCTION: Electromyostimulation (EMS) is an additional training stimulus to voluntary muscle activation, which was previously used for rehabilitation purposes only. However, its use has increasingly been shown to be able to optimize sports performance. The aim of this systematic review was to examine the effects of EMS training on physiological determinants of endurance performance in healthy subjects. EVIDENCE ACQUISITION: The aim of this systematic review was to examine the effects of EMS training on endurance-related performance parameters in healthy subjects. A systematic search of three databases (PubMed, SPORTDiscus, and Livivo), based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines was performed. Studies that included healthy subjects, electromyostimulation intervention with control group, physiological and endurance performance outcomes were assessed. The quality of studies was evaluated with the PEDro Scale. EVIDENCE SYNTHESIS: Full-text articles of 26 studies were reviewed and 11 fulfilled the inclusion criteria. The results revealed improvements in maximal oxygen uptake, oxygen uptake at ventilatory thresholds, running economy, and maximal lactate blood concentrations following EMS intervention; while maximum heart rate was not affected. Performance outcomes such as time-trial performance, time to exhaustion, and maximal work capacity also tended to be improved. CONCLUSIONS: The findings of this review conclude that electromyostimulation enhances oxygen uptake, running economy, lactate concentrations, and time-trial performance. Therefore, endurance could be improved in healthy individuals. Furthermore, its time efficiency advantages increase the potential and interest for further use and research. Nevertheless, methodological differences should be considered and more consensus in training programs is needed, to prove that electromyostimulation is beneficial regarding endurance parameters in healthy subjects.

Six weeks of whole-body vibration improves fine motor accuracy, functional mobility and quality of life in people with multiple sclerosis.

People with multiple sclerosis (MS) suffer from sensorimotor deficits with the distal extremities being more severely affected than proximal ones. Whole-body vibration (WBV) training is known to enhance voluntary activation and coordination in healthy people. However, evidence about beneficial effects of WBV in MS patients is scarce. The current study aimed to investigate if six weeks of WBV enhances motor function in the ankle joint, coordination and quality of life in patients suffering from severe MS. In a longitudinal design, changes in motor function and quality of life were assessed before and after a 6-week control period without a training (CON) and a 6-week WBV training (2-3x/week) in 15 patients (53 ±10 years) with advanced MS (EDSS 3-6.5). Before CON (t0), after CON (t1) and after WBV(t2), outcome measures included (1) active range of motion (aROM) and (2) motor accuracy at the ankle joint, (3) functional mobility (Timed "Up & Go" test with preferred and non-preferred turns) and (4) physical and psychological impact of MS (MSIS-29 questionnaire). For (1) and (2), the stronger (SL) and the weaker leg (WL) were compared. After WBV, aROM (1) did not change (SL p = 0.26, WL p = 0.10), but was diminished after CON (SL -10% p = 0.06, WL -14% p = 0.03) with significant group differences (Δgroup WL p = 0.02). Motor accuracy in SL (2) was improved during dorsal flexion after WBV (p = 0.01, Δgroup p = 0.04) and deteriorated during plantar flexion after CON (p = 0.01, Δgroup p = 0.04). Additionally, participants (3) improved their functional mobility at the preferred turn (p = 0.04) and (4) ranked their quality of life higher solely after WBV (p = 0.05), without any differences between groups. However, values correlated significantly between angular precision and aROM as well as functional mobility. No further changes occurred. The results point towards an interception of degenerating mono-articular mobility and improvement of accuracy in the ankle joint. The motor effects after WBV are in line with enhanced perception of quality of life after six weeks which is why WBV could be a stimulus to enable greater overall autonomy in MS patients.

Base editing repairs an SGCA mutation in human primary muscle stem cells.

Skeletal muscle can regenerate from muscle stem cells and their myogenic precursor cell progeny, myoblasts. However, precise gene editing in human muscle stem cells for autologous cell replacement therapies of untreatable genetic muscle diseases has not yet been reported. Loss-of-function mutations in SGCA, encoding α-sarcoglycan, cause limb-girdle muscular dystrophy 2D/R3, an early-onset, severe, and rapidly progressive form of muscular dystrophy affecting both male and female patients. Patients suffer from muscle degeneration and atrophy affecting the limbs, respiratory muscles, and heart. We isolated human muscle stem cells from 2 donors, with the common SGCA c.157G>A mutation affecting the last coding nucleotide of exon 2. We found that c.157G>A is an exonic splicing mutation that induces skipping of 2 coregulated exons. Using adenine base editing, we corrected the mutation in the cells from both donors with > 90% efficiency, thereby rescuing the splicing defect and α-sarcoglycan expression. Base-edited patient cells regenerated muscle and contributed to the Pax7+ satellite cell compartment in vivo in mouse xenografts. Here, we provide the first evidence to our knowledge that autologous gene-repaired human muscle stem cells can be harnessed for cell replacement therapies of muscular dystrophies.

Acute whole-body vibration reduces post-activation depression in the triceps surae muscle.

PURPOSE: Acute whole-body vibration (WBV) is known to enhance neuromuscular activation. Especially mechanisms which act presynaptically are discussed to be involved in this modulation, but evidence is still limited. Therefore, this study aimed to investigate if 2 min of WBV might impact the premotoneuronal mechanism of post-activation depression (PAD). METHODS: PAD in m. soleus was assessed by paired-pulse stimulation in 28 healthy participants prior, 2 min, 4 min and 10 min after 2 min of side-alternating WBV (10 Hz, 2 mm). Methodologies involved electromyography (m. soleus, m. tibialis anterior) and goniometric recordings (ankle, knee joint). H-reflexes were elicited with peripheral nerve stimulation and assessed by means of conditioned H-reflexes (ISI 1 s, Hcond) versus control H-reflexes (ISI10, H). RESULTS: Hcond/H was significantly enhanced by +55% (2 min), +32% (4 min) and +35% (10 min) following WBV (P < 0.05). Baseline muscle activity and joint positions were shown to be reliable (Cronbach's α values >0.990) throughout the testing procedure. CONCLUSION: Vibratory-induced spinal inhibition is accompanied by diminished PAD at the presynaptic terminals which interconnect the Ia afferents with the α-motoneuron. Functionally, the PAD reduction might explain enhanced motor performance following vibration therapy, but future studies will be needed to verify this assumption.

Whole-body vibration impedes the deterioration of postural control in patients with multiple sclerosis.

OBJECTIVE: The current study aimed to investigate if whole-body vibration (WBV) might attenuate the processing functional and neuromuscular degeneration of postural control in patients with MS. DESIGN: Performance in postural control was assessed before and after 6 weeks of a control (CON) and a WBV intervention period. SETTING: Laboratory at the University of Freiburg & home-based training PARTICIPANTS: Out of 29 interested participants, 15 subjects with severe MS fit inclusion criteria. MAIN OUTCOME MEASURES: Centre of pressure displacement (COP), muscle activity and co-contraction indices of m. soleus (SOL), gastrocnemius medialis (GM), tibialis anterior (TA), biceps (BF) and rectus femoris (RF) as well as SOL H/M-ratios. RESULTS: After CON, COP was significantly enhanced with reduced muscle activity in RF and diminished shank muscle co-contraction. After WBV, no changes were observed in COP and neuromuscular control. However, over time, TA activity was reduced, but with no changes in muscle activation of SOL, GM and BF or H/M-ratios. CONCLUSIONS: After CON, MS patients experienced substantial deteriorations in postural control which have previously been associated with greater postural instability. No further disease-associated deteriorations were observed following the intervention. Thus, WBV might alleviate neurodegeneration of postural control in people with MS.

The conserved histone chaperone LIN-53 is required for normal lifespan and maintenance of muscle integrity in Caenorhabditis elegans.

Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and aspects of healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) associates with different chromatin-regulating complexes to safeguard cell identities in Caenorhabditis elegans as well as mammals, and has a role in preventing memory loss and premature aging in humans. We show that LIN-53 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in C. elegans muscles to ensure functional muscles during postembryonic development and in adults. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolomic analysis revealing that levels of the disaccharide trehalose are significantly decreased in both mutants. As trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with trehalose or increasing trehalose levels via the insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and muscle integrity through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan regulation is also evolutionarily conserved.

Vibration therapy in patients with cerebral palsy: a systematic review.

The neurological disorder cerebral palsy (CP) is caused by unprogressive lesions of the immature brain and affects movement, posture, and the musculoskeletal system. Vibration therapy (VT) is increasingly used to reduce the signs and symptoms associated with this developmental disability. The purpose of this narrative review was systematically to appraise published research regarding acute and long-term effects of VT on functional, neuromuscular, and structural parameters. Systematic searches of three electronic databases identified 28 studies that fulfilled the inclusion criteria. Studies were analyzed to determine participant characteristics, VT-treatment protocols, effect on gross motor function (GMF), strength, gait, posture, mobility, spasticity, reflex excitability, muscle tone, mass, and bone strength within this population, and outcome measures used to evaluate effects. The results revealed that one acute session of VT reduces reflex excitability, spasticity, and coordination deficits. Subsequently, VT has a positive effect on the ability to move, manifested for GMF, strength, gait, and mobility in patients with CP. Effects persist up to 30 minutes after VT. Long-term effects of VT manifest as reduced muscle tone and spasticity occurring concomitantly with improved movement ability in regard to GMF, strength, gait, and mobility, as well as increased muscle mass and bone-mineral density. Posture control remained unaffected by VT. In conclusion, the acute and chronic application of VT as a nonpharmacological approach has the potential to ameliorate CP symptoms, achieving functional and structural adaptations associated with significant improvements in daily living. Even though further studies including adult populations validating the neuromuscular mechanisms underlying the aforementioned adaptations should be fostered, growing scientific evidence supports the effectiveness of VT in regard to supplementing conventional treatments (physiotherapy and drugs). Therefore, VT could reduce CP-associated physical disability and sensorimotor handicaps. Goals for patients and their caregivers referring to greater independence and improved safety may be achieved more easily and time efficiently.

Acute whole-body vibration increases reciprocal inhibition.

Based on previous evidence that whole-body vibration (WBV) affects pathways involved in disynaptic reciprocal inhibition (DRI), the present hypothesis-driven experiment aimed to assess the acute effects of WBV on DRI and co-contraction. DRI from ankle dorsiflexors to plantar flexors was investigated during submaximal dorsiflexion before and after 1 min of WBV. With electromyography, musculus soleus (SOL) H-reflex depression following a conditioning stimulation of the peroneal nerve (1.1x motor threshold for the musculus tibialis anterior, TA) was assessed and co-contraction was calculated. After WBV, DRI was significantly increased (+4%, p < 0.05). SOL (-13%, p < 0.05) and TA (-6%, p < 0.05) activities were significantly reduced; co-contraction tended to be diminished (-8%, p = 0.05). Dorsiflexion torque remained unchanged. After WBV, DRI increased during submaximal isometric contraction in healthy subjects. The simultaneous SOL relaxation and TA contraction indicate that a more economic movement execution is of functional significance for WBV application in clinical and athletic treatment.

Stimulus Prediction and Postural Reaction: Phase-Specific Modulation of Soleus H-Reflexes Is Related to Changes in Joint Kinematics and Segmental Strategy in Perturbed Upright Stance.

Anticipation determines the timing and efficiency of human motor performance. This study aimed to evaluate the effect of stimulus anticipation on proactive (prior to the event) and reactive (after the event) postural adjustments in response to perturbations. Postural set was manipulated by providing either (i) predictable, (ii) unpredictable, or (iii) cheated perturbations which require balance corrections to maintain postural stability. In 29 subjects, a protocol of anterior and posterior perturbations was applied for the conditions (i-iii). Center of pressure (COP) displacement, ankle, knee, and hip joint kinematics and electromyographic activity (EMG) of the soleus (SOL) and tibialis anterior (TA) muscles were recorded prior (PRE) and after posterior perturbations. SOL H-reflexes at the peak of the short-, medium- ,and long-latency responses (SLR, MLR, LLR) were assessed. For conditions (i to iii) EMG activity and COP differed prior to perturbation onset (p < 0.05). After perturbation, results demonstrated a progressively increased H-reflex amplitude in the MLR and LLR (p < 0.05), delayed muscle activities (p < 0.05), and shifted activation patterns, with muscles of the proximal segment being more involved in the compensatory postural response (p < 0.05). COP displacements and ankle, knee, and hip joint deflections progressively increased (p < 0.05). Neuromechanical coupling showed positive correlations for the anticipation-induced changes in EMG activity and H-reflex amplitude with that of COP displacement (p < 0.05). In conclusion, proactive and reactive postural responses indicated setting dependent modulations of segmental and phasic muscle activation. A shift to proximal muscle groups and facilitated late reflex responses compensating for cheated or unpredicted perturbations was found to recover a safe body equilibrium. In consideration of the phase-specific adaptation and its interrelationship to the kinematics, it suggested that changes in stimulus prediction challenged the central nervous system to appropriately counteract the higher postural challenges. The outcomes of this experiment are of functional relevance for experimental and training settings involving perturbation stimuli. These findings provide fundamental information of the mechanisms underlying postural adjustments in response to external perturbations.

Neuromuscular and Kinematic Adaptation in Response to Reactive Balance Training - a Randomized Controlled Study Regarding Fall Prevention.

Slips and stumbles are main causes of falls and result in serious injuries. Balance training is widely applied for preventing falls across the lifespan. Subdivided into two main intervention types, biomechanical characteristics differ amongst balance interventions tailored to counteract falls: conventional balance training (CBT) referring to a balance task with a static ledger pivoting around the ankle joint versus reactive balance training (RBT) using externally applied perturbations to deteriorate body equilibrium. This study aimed to evaluate the efficacy of reactive, slip-simulating RBT compared to CBT in regard to fall prevention and to detect neuromuscular and kinematic dependencies. In a randomized controlled trial, 38 participants were randomly allocated either to CBT or RBT. To simulate stumbling scenarios, postural responses were assessed to posterior translations in gait and stance perturbation before and after 4 weeks of training. Surface electromyography during short- (SLR), medium- (MLR), and long-latency response of shank and thigh muscles as well as ankle, knee, and hip joint kinematics (amplitudes and velocities) were recorded. Both training modalities revealed reduced angular velocity in the ankle joint (P < 0.05) accompanied by increased shank muscle activity in SLR (P < 0.05) during marching in place perturbation. During stance perturbation and marching in place perturbation, hip angular velocity was decreased after RBT (P from TTEST, Pt < 0.05) accompanied by enhanced thigh muscle activity (SLR, MLR) after both trainings (P < 0.05). Effect sizes were larger for the RBT-group during stance perturbation. Thus, both interventions revealed modified stabilization strategies for reactive balance recovery after surface translations. Characterized by enhanced reflex activity in the leg muscles antagonizing the surface translations, balance training is associated with improved neuromuscular timing and accuracy being relevant for postural control. This may result in more efficient segmental stabilization during fall risk situations, independent of the intervention modality. More pronounced modulations and higher effect sizes after RBT in stance perturbation point toward specificity of training adaptations, with an emphasis on the proximal body segment for RBT. Outcomes underline the benefits of balance training with a clear distinction between RBT and CBT being relevant for training application over the lifespan.

Alleviation of Motor Impairments in Patients with Cerebral Palsy: Acute Effects of Whole-body Vibration on Stretch Reflex Response, Voluntary Muscle Activation and Mobility.

INTRODUCTION: Individuals suffering from cerebral palsy (CP) often have involuntary, reflex-evoked muscle activity resulting in spastic hyperreflexia. Whole-body vibration (WBV) has been demonstrated to reduce reflex activity in healthy subjects, but evidence in CP patients is still limited. Therefore, this study aimed to establish the acute neuromuscular and kinematic effects of WBV in subjects with spastic CP. METHODS: 44 children with spastic CP were tested on neuromuscular activation and kinematics before and immediately after a 1-min bout of WBV (16-25 Hz, 1.5-3 mm). Assessment included (1) recordings of stretch reflex (SR) activity of the triceps surae, (2) electromyography (EMG) measurements of maximal voluntary muscle activation of lower limb muscles, and (3) neuromuscular activation during active range of motion (aROM). We recorded EMG of m. soleus (SOL), m. gastrocnemius medialis (GM), m. tibialis anterior, m. vastus medialis, m. rectus femoris, and m. biceps femoris. Angular excursion was recorded by goniometry of the ankle and knee joint. RESULTS: After WBV, (1) SOL SRs were decreased (p < 0.01) while (2) maximal voluntary activation (p < 0.05) and (3) angular excursion in the knee joint (p < 0.01) were significantly increased. No changes could be observed for GM SR amplitudes or ankle joint excursion. Neuromuscular coordination expressed by greater agonist-antagonist ratios during aROM was significantly enhanced (p < 0.05). DISCUSSION: The findings point toward acute neuromuscular and kinematic effects following one bout of WBV. Protocols demonstrate that pathological reflex responses are reduced (spinal level), while the execution of voluntary movement (supraspinal level) is improved in regards to kinematic and neuromuscular control. This facilitation of muscle and joint control is probably due to a reduction of spasticity-associated spinal excitability in favor of giving access for greater supraspinal input during voluntary motor control.

Specific Stimuli Induce Specific Adaptations: Sensorimotor Training vs. Reactive Balance Training.

Typically, balance training has been used as an intervention paradigm either as static or as reactive balance training. Possible differences in functional outcomes between the two modalities have not been profoundly studied. The objective of the study was to investigate the specificity of neuromuscular adaptations in response to two balance intervention modalities within test and intervention paradigms containing characteristics of both profiles: classical sensorimotor training (SMT) referring to a static ledger pivoting around the ankle joint vs. reactive balance training (RBT) using externally applied perturbations to deteriorate body equilibrium. Thirty-eight subjects were assigned to either SMT or RBT. Before and after four weeks of intervention training, postural sway and electromyographic activities of shank and thigh muscles were recorded and co-contraction indices (CCI) were calculated. We argue that specificity of training interventions could be transferred into corresponding test settings containing properties of SMT and RBT, respectively. The results revealed that i) postural sway was reduced in both intervention groups in all test paradigms; magnitude of changes and effect sizes differed dependent on the paradigm: when training and paradigm coincided most, effects were augmented (P<0.05). ii) These specificities were accompanied by segmental modulations in the amount of CCI, with a greater reduction within the CCI of thigh muscles after RBT compared to the shank muscles after SMT (P<0.05). The results clearly indicate the relationship between test and intervention specificity in balance performance. Hence, specific training modalities of postural control cause multi-segmental and context-specific adaptations, depending upon the characteristics of the trained postural strategy. In relation to fall prevention, perturbation training could serve as an extension to SMT to include the proximal segment, and thus the control of structures near to the body's centre of mass, into training.

Bouncing on Mars and the Moon-the role of gravity on neuromuscular control: correlation of muscle activity and rate of force development.

On our astronomical neighbors Mars and the Moon, bouncing movements are the preferred locomotor techniques. During bouncing, the stretch-shortening cycle describes the muscular activation pattern. This study aimed to identify gravity-dependent changes in kinematic and neuromuscular characteristics in the stretch-shortening cycle. Hence, neuromuscular control of limb muscles as well as correlations between the muscles' pre-activation, reflex components, and force output were assessed in lunar, Martian, and Earth gravity. During parabolic flights, peak force (Fmax), ground-contact-time, rate of force development (RFD), height, and impulse were measured. Electromyographic (EMG) activities in the m. soleus (SOL) and gastrocnemius medialis (GM) were assessed before (PRE) and during bounces for the reflex phases short-, medium-, and long-latency response (SLR, MLR, LLR). With gradually decreasing gravitation, Fmax, RFD, and impulse were reduced, whereas ground-contact time and height increased. Concomitantly, EMG_GM decreased for PRE, SLR, MLR, and LLR, and in EMG_SOL in SLR, MLR, and LLR. For SLR and MLR, Fmax and RFD were positively correlated to EMG_SOL. For PRE and LLR, RFD and Fmax were positively correlated to EMG_GM. Findings emphasize that biomechanically relevant kinematic adaptations in response to gravity variation were accompanied by muscle- and phase-specific modulations in neural control. Gravitational variation is anticipated and compensated for by gravity-adjusted muscle activities. Importantly, the pre-activation and reflex phases were differently affected: in SLR and MLR, SOL is assumed to contribute to the decline in force output with a decreasing load, and, complementary in PRE and LLR, GM seems to be of major importance for force generation.

Load Dependency of Postural Control--Kinematic and Neuromuscular Changes in Response to over and under Load Conditions.

INTRODUCTION: Load variation is associated with changes in joint torque and compensatory reflex activation and thus, has a considerable impact on balance control. Previous studies dealing with over (OL) and under loading (UL) used water buoyancy or additional weight with the side effects of increased friction and inertia, resulting in substantially modified test paradigms. The purpose of this study was to identify gravity-induced load dependency of postural control in comparable experimental conditions and to determine the underlying neuromuscular mechanisms. METHODS: Balance performance was recorded under normal loading (NL, 1 g), UL (0.16 g 0.38 g) and OL (1.8 g) in monopedal stance. Center of pressure (COP) displacement and frequency distribution (low 0.15-0.5 Hz (LF), medium 0.5-2 Hz (MF), high 2-6 Hz (HF)) as well as ankle, knee and hip joint kinematics were assessed. Soleus spinal excitability was determined by H/M-recruitment curves (H/M-ratios). RESULTS: Compared to NL, OL caused an increase in ankle joint excursion, COP HF domain and H/M-ratio. Concomitantly, hip joint excursion and COP LF decreased. Compared to NL, UL caused modulations in the opposite direction: UL decreased ankle joint excursions, COP HF and H/M-ratio. Collaterally, hip joint excursion and COP LF increased. COP was augmented both in UL and in OL compared to NL. CONCLUSION: Subjects achieved postural stability in OL and UL with greater difficulty compared to NL. Reduced postural control was accompanied by modified balance strategies and compensatory reflex activation. With increasing load, a shift from hip to ankle strategy was observed. Accompanying, COP frequency distribution shifted from LF to HF and spinal excitability was enhanced. It is suggested that in OL, augmented ankle joint torques are compensated by quick reflex-induced postural reactions in distal muscles. Contrarily, UL is associated with diminished joint torques and thus, postural equilibrium may be controlled by the proximal segments to adjust the center of gravity above the base of support.