Human muscle and spinal activation in response to body weight loading.

Human standing is the anatomical and functional framework for independent movement. The study of weight bearing during standing and movement is crucial to support the development of technology aimed at restoring independent gait, where unsupported weight bearing is still elusive. This study aims to determine muscle and spinal activation at different gravitational loads in young, healthy individuals to provide potential patterns of spinal stimulation for standing. Muscle activity was recorded with surface electromyography (EMG) from 18 healthy participants at different body angles while on a motorised plinth. The body angles tested and the relative gravitational loadings were: 0 deg (supine) corresponding to ~0% of total body weight (BW), 15 deg (~26% BW), 30 deg (~50% BW), 45 deg (~71% BW), 60 deg (~87% BW), 75 deg (~97% BW), upright on and off the plinth (~100% BW). The muscles recorded were soleus, gastrocnemius medialis and lateralis, tibialis anterior, adductor longus, peroneus longus, vastus medialis and lateralis, rectus femoris, sartorius, extensor digitorum longus, semimembranosus, semitendinosus, biceps femoris, gracilis, rectus abdominis, external oblique, erector spinae and latissimus dorsi. From the recorded muscle activity, spinal activation maps were calculated. Despite high variability in EMG data, the group muscle activity changed with body angle. Vastus lateralis became activated at 60 deg (~87% BW), soleus became activated at 75 deg, and the gastrocnemii at 90 deg. The spinal segments that showed significant differences in mean activation between angles were the fifth lumbar L5 and the first sacral S1 segments. The data from this study suggest that weight-bearing independent standing could be achieved with increased activation of a limited number of superficial muscles tested, and 87% BW is a critical loading for increased muscle activation compared to the supine position. The spinal activation in the lower lumbar and sacral segments shows the involvement of these regions in maintaining weight-bearing standing. By reproducing this pattern of muscle and spinal segment activity through tonic stimulation, we speculate that restoration of independent standing and walking may be possible for patients following spinal cord injuries.

A Probabilistic Model of Human Activity Recognition with Loose Clothing.

Human activity recognition has become an attractive research area with the development of on-body wearable sensing technology. Textiles-based sensors have recently been used for activity recognition. With the latest electronic textile technology, sensors can be incorporated into garments so that users can enjoy long-term human motion recording worn comfortably. However, recent empirical findings suggest, surprisingly, that clothing-attached sensors can actually achieve higher activity recognition accuracy than rigid-attached sensors, particularly when predicting from short time windows. This work presents a probabilistic model that explains improved responsiveness and accuracy with fabric sensing from the increased statistical distance between movements recorded. The accuracy of the comfortable fabric-attached sensor can be increased by 67% more than rigid-attached sensors when the window size is 0.5s. Simulated and real human motion capture experiments with several participants confirm the model's predictions, demonstrating that this counterintuitive effect is accurately captured.

Visual field motion during a body pull affects compensatory standing and stepping responses.

KEY POINTS: It is unclear whether the visual input that accompanies a perturbation of a standing person can affect whether a recovery step is taken. Visual motion speeds were manipulated during unexpected forward and backward shoulder pulls. Visual motion that appeared slower than actual body motion reduced the initial in-place resistance to the perturbation. As a result of the modulation of the in-place response, less pull force was needed to trigger a step when visual velocity appeared slower than normal. The visuomotor postural response occurred earlier and was larger when the full-field visual input was paired with a mechanical perturbation. ABSTRACT: The present study aimed to determine how visual motion evoked by an upper body perturbation during standing affects compensatory postural responses. This was investigated by rotating the visual field forwards or backwards about the ankle, time-locked to a forwards or backwards shoulder pull. Kinematic, kinetic and electromyographic responses were recorded to a range of pull forces over 160 trials in 12 healthy adults (mean ± SD = 31 ± 5.8 years). Stepping threshold forces and in-place postural responses were compared between conditions. When the visual field moved in the same direction as the pull, so that the apparent velocity of the body was reduced (SLOW condition), the pull-force required to induce a step was less than when the visual field either rotated in the opposite direction (FAST) or was unaltered (NATURAL). For in-place responses, the body was displaced further in the direction of the pull in the SLOW condition. This was the result of a reduction in the resistive force from lower leg muscles 130 ms after the visual motion onset. In trials with no pull, the visual motion induced postural responses that were later (290 ms) and had smaller amplitudes compared to when visual motion is paired with an unexpected perturbation of the body. The results suggest that the apparent speed of the visual environment during a perturbation does influence whether a compensatory step is taken, not via a direct effect on the decision to step but by modulating the initial in-place response.

Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e., before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers' muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.-Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

Dual processing of visual rotation for bipedal stance control.

KEY POINTS: When standing, the gain of the body-movement response to a sinusoidally moving visual scene has been shown to get smaller with faster stimuli, possibly through changes in the apportioning of visual flow to self-motion or environment motion. We investigated whether visual-flow speed similarly influences the postural response to a discrete, unidirectional rotation of the visual scene in the frontal plane. Contrary to expectation, the evoked postural response consisted of two sequential components with opposite relationships to visual motion speed. With faster visual rotation the early component became smaller, not through a change in gain but by changes in its temporal structure, while the later component grew larger. We propose that the early component arises from the balance control system minimising apparent self-motion, while the later component stems from the postural system realigning the body with gravity. ABSTRACT: The source of visual motion is inherently ambiguous such that movement of objects in the environment can evoke self-motion illusions and postural adjustments. Theoretically, the brain can mitigate this problem by combining visual signals with other types of information. A Bayesian model that achieves this was previously proposed and predicts a decreasing gain of postural response with increasing visual motion speed. Here we test this prediction for discrete, unidirectional, full-field visual rotations in the frontal plane of standing subjects. The speed (0.75-48 deg s(-1) ) and direction of visual rotation was pseudo-randomly varied and mediolateral responses were measured from displacements of the trunk and horizontal ground reaction forces. The behaviour evoked by this visual rotation was more complex than has hitherto been reported, consisting broadly of two consecutive components with respective latencies of ∼190 ms and >0.7 s. Both components were sensitive to visual rotation speed, but with diametrically opposite relationships. Thus, the early component decreased with faster visual rotation, while the later component increased. Furthermore, the decrease in size of the early component was not achieved by a simple attenuation of gain, but by a change in its temporal structure. We conclude that the two components represent expressions of different motor functions, both pertinent to the control of bipedal stance. We propose that the early response stems from the balance control system attempting to minimise unintended body motion, while the later response arises from the postural control system attempting to align the body with gravity.

Maintaining balance against force perturbations: impaired mechanisms unresponsive to levodopa in Parkinson's disease.

There is evidence that postural instability associated with Parkinson's disease (PD) is not adequately improved by levodopa, implying involvement of nondopaminergic pathways. However, the mechanisms contributing to postural instability have yet to be fully identified and tested for their levodopa responsiveness. In this report we investigate balance processes that resist external forces to the body when standing. These include in-place responses and the transition to protective stepping. Forward and backward shoulder pulls were delivered using two force-feedback-controlled motors and were randomized for direction, magnitude, and onset. Sixteen patients with PD were tested OFF and ON levodopa, and 16 healthy controls were tested twice. Response behavior was quantified from 3-dimensional ground reaction forces and kinematic measurements of body segments and total body center-of-mass (CoM) motion. In-place responses resisting the pull were significantly smaller in PD as reflected in reduced horizontal anteroposterior ground reaction force and increased CoM displacement. Ankle, knee, and hip moments contributing to this resistance were smaller in PD, with the knee extensor moment to backward pulls being the most affected. The threshold force needed to evoke a step was also smaller for PD in the forward direction. Protective steps evoked by suprathreshold pulls showed deficits in PD in the backward direction, with steps being shorter and more steps being required to arrest the body. Levodopa administration had no significant effect on either in-place or protective stepping deficits. We conclude that processes employed to maintain balance in the face of external forces show impairment in PD consistent with disruption to nondopaminergic systems.

Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences.

Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.

Sex differences in alpha-synucleinopathies: a systematic review.

Background: Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach. Methods: In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid. Results: One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects. Conclusion: Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.

Mobile phone use is detrimental for gait stability in young adults.

BACKGROUND: Human walking is a highly automated motor task, however if the individual's attention is divided, gait can be negatively affected. Although the effect of divided attention has been usually tested with standardised cognitive tasks, the common task of walking while talking on the phone may represent an ecological dual task scenario. RESEARCH QUESTION: What is the effect of divided attention on locomotion when using a mobile phone? METHODS: Thirty-seven healthy participants were asked to walk while performing different cognitive tasks: counting and spelling backwards, talking on the phone (handset by the ear and hands-free), and texting. As a control, extra postural conditions were tested: holding the phone by the ear (without talking) and carrying the phone as in the texting task. These tasks were compared with normal walking (no other cognitive or postural task). Twenty participants also performed the same tasks with the addition of an obstacle halfway through the walkway. Gait performance was measured using non-invasive inertial sensors. Step time and mediolateral acceleration range were calculated. RESULTS: Step time increased when counting (mean ± standard error 0.63 ± 0.02 s, p < 0.001), spelling backwards (0.67 ± 0.03 s, p < 0.001) and texting (0.61 ± 0.02 s, p = 0.005) compared to normal walking (0.56 ± 0.02 s). Compared to normal walking (8.03 ± 0.58 m/s2), mediolateral acceleration decreased when counting (6.43 ± 0.39 m/s2, p < 0.001), spelling backwards (6.67 ± 0.44 m/s2, p < 0.001), when talking on the phone while holding the phone (7.28 ± 0.48 m/s2, p = 0.003), or hands-free (7.28 ± 0.40 m/s2, p = 0.004), or texting (6.71 ± 0.50 m/s2, p < 0.001). Introducing an obstacle confirmed these results. SIGNIFICANCE: This study shows that even in young and healthy individuals, gait is affected by divided attention. Furthermore, the results show that common and ecological cognitive tasks, such as phone use, could induce measurable worsening of gait performance. Individuals should be careful when walking and performing other tasks that could distract them, by dividing their attention.

Methodological considerations in measuring specific force in human single skinned muscle fibres.

Chemically skinned fibres allow the study of human muscle contractile function in vitro. A particularly important parameter is specific force (SF), that is, maximal isometric force divided by cross-sectional area, representing contractile quality. Although SF varies substantially between studies, the magnitude and cause of this variability remains puzzling. Here, we aimed to summarize and explore the cause of variability in SF between studies. A systematic search was conducted in Medline, Embase and Web of Science databases in June 2020, yielding 137 data sets from 61 publications which studied healthy, young adults. Five-fold differences in mean SF data were observed. Adjustments to the reported data for key methodological differences allowed between-study comparisons to be made. However, adjustment for fibre shape, swelling and sarcomere length failed to significantly reduce SF variance (I2 = 96%). Interestingly, grouping papers based on shared authorship did reveal consistency within research groups. In addition, lower SF was found to be associated with higher phosphocreatine concentrations in the fibre activating solution and with Triton X-100 being used as a skinning agent. Although the analysis showed variance across the literature, the ratio of SF in single fibres containing myosin heavy chain isoforms IIA or I was found to be consistent across research groups. In conclusion, whilst the skinned fibre technique is reliable for studying in vitro force generation of single fibres, the composition of the solution used to activate fibres, which differs between research groups, is likely to heavily influence SF values.

Mobile phone use impairs stair gait: A pilot study on young adults.

Human movement control requires attention to accurately tune motor commands in response to environmental changes. Dual task paradigms are used to test the role of attention on motor performance. Usually the tasks used have little resemblance with every day experience. Here we ask: Does a common cognitive task, such as a mobile phone conversation, compromise motor performance on stairs? Eight young participants negotiated an instrumented seven-step staircase. Stair negotiation while talking on a mobile phone was compared to normal stair negotiation. Stepping parameters, jerk cost (measure of smoothness of locomotion) and step clearance were measured. When talking on a mobile phone, participants' overall body velocity (mean(sd): Ascent 0.534(0.026) vs 0.511(0.024) m/s, Descent 0.642(0.026) vs 0.511(0.024) m/s, No phone/Phone respectively) and cadence decreased significantly (Ascent 75.8(5.8) vs 65.6(4.4) steps/min, Descent 117.4(4.2) vs 108.6(6.0) steps/min, No Phone/Phone respectively). Pelvis and feet jerk cost also changed significantly, mostly decreasing with phone use. Foot clearance did not show significant changes between No Phone and Phone conditions. These pilot results show that, even for young, healthy and cognitively intact individuals, talking on a mobile phone whilst negotiating a staircase induces measurable changes in motor performance. Participants moved slowly but more smoothly, reducing the motor control cost, possibly at the expense of movement accuracy. The reduction in motor performance is likely to be due to the difficulty in integrating the two sub-tasks. These results suggest that even young, healthy individuals show stair gait impairment when simultaneously negotiating stairs and performing another cognitive task, such as talking on the phone.

Stair Gait in Older Adults Worsens With Smaller Step Treads and When Transitioning Between Level and Stair Walking.

Older people have an increased risk of falling during locomotion, with falls on stairs being particularly common and dangerous. Step going (i.e., the horizontal distance between two consecutive step edges) defines the base of support available for foot placement on stairs, as with smaller going, the user's ability to balance on the steps may become problematic. Here we quantified how stair negotiation in older participants changes between four goings (175, 225, 275, and 325 mm) and compared stair negotiation with and without a walking approach. Twenty-one younger (29 ± 6 years) and 20 older (74 ± 4 years) participants negotiated a 7-step experimental stair. Motion capture and step-embedded force platform data were collected. Handrail use was also monitored. From the motion capture data, body velocity, trunk orientation, foot clearance and foot overhang were quantified. For all participants, as stair going decreased, gait velocity (ascent pA = 0.033, descent pD = 0.003) and horizontal step clearance decreased (pA = 0.001), while trunk rotation (pD = 0.002) and foot overhang increased (pA,D < 0.001). Compared to the younger group, older participants used the handrail more, were slower across all conditions (pA < 0.001, pD = 0.001) and their foot clearance tended to be smaller. With a walking approach, the older group (Group x Start interaction) showed a larger trunk rotation (pA = 0.011, pD = 0.015), and smaller lead foot horizontal (pA = 0.046) and vertical clearances (pD = 0.039) compared to the younger group. A regression analysis to determine the predictors of foot clearance and amount of overhang showed that physical activity was a common predictor for both age groups. In addition, for the older group, medications and fear of falling were found to predict stair performance for most goings, while sway during single-legged standing was the most common predictor for the younger group. Older participants adapted to smaller goings by using the handrails and reducing gait velocity. The predictors of performance suggest that motor and fall risk assessment is complex and multifactorial. The results shown here are consistent with the recommendation that larger going and pausing before negotiating stairs may improve stair safety, especially for older users.

The proprioceptive and agonist roles of gastrocnemius, soleus and tibialis anterior muscles in maintaining human upright posture.

Humans can stand using sensory information solely from the ankle muscles. Muscle length and tension in the calf muscles (gastrocnemius and soleus) are unlikely to signal postural sways on account of balance-related modulation in agonist activity. These facts pose two questions: (1) Which ankle muscles provide the proprioceptive information? (2) Which peripheral mechanism could modulate agonist activity? To address these issues, subjects were asked to stand normally on two force plates. Ultrasound and surface EMG were recorded from the calf and tibialis anterior (TA) muscles. For all nine subjects, changes in muscle length of TA were mainly (84 +/- 9% whole trial duration) orthodoxly correlated with bodily sway (centre of gravity, CoG), i.e. in accordance with passive ankle rotation. When orthodox, TA had the highest correlation with CoG (-0.66 +/- 0.07, deep compartment, P < 0.001). For five subjects, the superficial TA compartment showed counter-intuitive changes in muscle length with CoG, probably due to the flattening of the foot and proximal attachment geometry. Gastrocnemius and soleus were usually (duration 71 +/- 23 and 81 +/- 16%, respectively) active agonists (paradoxically correlated with CoG) but, for short periods of time, they could be orthodox and then presented a moderate correlation (0.38 +/- 0.16 and 0.28 +/- 0.09, respectively) with CoG. Considering the duration and extent to which muscle length is orthodox and correlated with CoG, TA may be a better source of proprioceptive information than the active agonists (soleus and gastrocnemius). Therefore, if a peripheral feedback mechanism modulates agonist activity then reciprocal inhibition acted by TA on the calf muscles is more likely to be effective than the autogenic pathway.

Attainment of Quiet Standing in Humans: Are the Lower Limb Joints Controlled Relative to a Misaligned Postural Reference?

In human quiet standing, the relative position between ankle joint centre and line of gravity is neurally regulated within tight limits. The regulation of the knee and hip configuration is unclear and thought to be controlled passively. However, perturbed standing experiments have shown a lower limb multi-joint coordination. Here, measuring the relative alignment between lower limb joints and the line of gravity in quiet standing after walking, we investigated whether the configuration is maintained over time through passive mechanisms or active control. Thirteen healthy adults walked without following a path and then stood quietly for 7.6 s on a force platform (up to four trials). The transition between initiation and steady-state standing (7.6 s) was measured using motion capture. Sagittal lower limb joint centres' position relative to line of gravity (CoGAP) and their time constants were calculated in each trial. Ankle, knee, and hip joint moments were also calculated through inverse dynamics. After walking, the body decelerated (τ = 0.16 s). The ankle and hip joints' position relative to CoGAP measured at two time intervals of quiet standing (Mid = 0.5-0.55 s; End = 7.55-7.6 s) were different (mean ± SEM, CoGAP-Ankle_Mid = 47 ± 4 mm, CoGAP-Ankle_End = 58 ± 5 mm; CoGAP-Hip_Mid = 2 ± 5 mm, CoGAP-Hip_End = -5 ± 5 mm). The ankle, knee, and hip flexion-extension moments significantly changed. Changes in joints position relative to CoGAP and misalignment suggest that joint position is not maintained over 7.6 s, but regulated relative to a standing reference. Higher joint moments at steady-state standing suggest mechanisms other than passive knee and hip regulation are involved in standing.

Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease: Optimal Frequency for Gait Depends on Stimulation Site and Axial Symptoms.

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40-140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.

Sarcolab pilot study into skeletal muscle's adaptation to long-term spaceflight.

Spaceflight causes muscle wasting. The Sarcolab pilot study investigated two astronauts with regards to plantar flexor muscle size, architecture, and function, and to the underlying molecular adaptations in order to further the understanding of muscular responses to spaceflight and exercise countermeasures. Two crew members (A and B) spent 6 months in space. Crew member A trained less vigorously than B. Postflight, A showed substantial decrements in plantar flexor volume, muscle architecture, in strength and in fiber contractility, which was strongly mitigated in B. The difference between these crew members closely reflected FAK-Y397 abundance, a molecular marker of muscle's loading history. Moreover, crew member A showed downregulation of contractile proteins and enzymes of anaerobic metabolism, as well as of systemic markers of energy and protein metabolism. However, both crew members exhibited decrements in muscular aerobic metabolism and phosphate high energy transfer. We conclude that countermeasures can be effective, particularly when resistive forces are of sufficient magnitude. However, to fully prevent space-related muscular deterioration, intersubject variability must be understood, and intensive exercise countermeasures programs seem mandatory. Finally, proteomic and metabolomic analyses suggest that exercise benefits in space may go beyond mere maintenance of muscle mass, but rather extend to the level of organismic metabolism.

Erratum: Author Correction: Sarcolab pilot study into skeletal muscle's adaptation to longterm spaceflight.

[This corrects the article DOI: 10.1038/s41526-018-0052-1.].

Human standing: does the control strategy preprogram a rigid knee?

Human standing requires control of multisegmental configuration. Does the postural system normally allow flexible adjustment of configuration, or does it minimize degrees of freedom at the ankle, knee, and hip joints? Gentle, external, unpredictable, sagittal, mechanical perturbations (randomized force, 1-10 N; duration, 0.2-2 s; and leg) were applied to either knee of 24 healthy participants who stood symmetrically for 200 s. The translation of knee perturbation force to ankle, knee, and hip joint rotations in the perturbed and unperturbed legs was studied. We assessed whether consequent joint rotations indicated a stiff configuration-conserving or viscous energy-absorbing relationship to the knee perturbation. Two distinctive response patterns were observed. Twenty-two participants showed limited knee flexion and high ankle stiffness, whereas two participants showed substantial knee flexion, low ankle stiffness, measurable internal rotation of the unperturbed hip (0.4 ± 0.3 vs. 3.0 ± 1°, 5.7 ± 17 vs. 0.5 ± 0.3 N/°, 1.1 ± 0.4°, respectively; mean ± SD), and a viscous relationship between perturbation force and subsequent ankle flexion, knee flexion, and perturbed and unperturbed hip internal rotation. The size of knee-flexion response to knee perturbations was uncorrelated with the extent of unperturbed standing sway. Normal standing conceals a large interindividual range in leg control strategies, indicating adaptive potential to progress with development and skill acquisition and decline with age, disease, injury, and fear. Commonly, leg configuration was maintained stiffly. Less commonly, a bilateral, low-stiffness, energy-absorbing strategy utilizing the available degrees of freedom was shown. We propose that identification of individual coordination strategy has diagnostic and prognostic potential in relation to perceptual-posture-movement-fall interactions.

The consequences of short-range stiffness and fluctuating muscle activity for proprioception of postural joint rotations: the relevance to human standing.

Proprioception comes from muscles and tendons. Tendon compliance, muscle stiffness, and fluctuating activity complicate transduction of joint rotation to a proprioceptive signal. These problems are acute in postural regulation because of tiny joint rotations and substantial short-range muscle stiffness. When studying locomotion or perturbed balance these problems are less applicable. We recently measured short-range stiffness in standing and considered the implications for load stability. Here, using an appropriately simplified model we analyze the conversion of joint rotation to spindle input and tendon tension while considering the effect of short-range stiffness, tendon compliance, fluctuating muscle activity, and fusimotor activity. Basic principles determine that when muscle stiffness and tendon compliance are high, fluctuating muscle activity is the greatest factor confounding registration of postural movements, such as ankle rotations during standing. Passive and isoactive muscle, uncomplicated by active length fluctuations, enable much better registration of joint rotation and require fewer spindles. Short-range muscle stiffness is a degrading factor for spindle input and enhancing factor for Golgi input. Constant fusimotor activity does not enhance spindle registration of postural joint rotations in actively modulated muscle: spindle input remains more strongly associated with muscle activity than joint rotation. A hypothesized rigid alpha-gamma linkage could remove this association with activity but would require large numbers of spindles in active postural muscles. Using microneurography, the existence of a rigid alpha-gamma linkage could be identified from the correlation between spindle output and muscle activity. Basic principles predict a proprioceptive "dead zone" in the active agonist muscle that is related to the short-range muscle stiffness.