The addition of the MEP amplitude of finger extension muscles to clinical predictors of hand function after stroke: A prospective cohort study.

BACKGROUND: Within the first 72 hours after stroke, active finger extension is a strong predictor of long-term dexterity. Transcranial magnetic stimulation may add prognostic value to clinical assessment, which is especially relevant for patients unable to follow instructions. OBJECTIVE: The current prospective cohort study aims at determining whether amplitude of motor evoked potentials of the extensor digitorum communis (EDC) can improve clinical prediction after stroke when added to clinical tests. METHODS: the amplitude of motor evoked potentials of the affected EDC muscle at rest was measured in 18 participants within 4 weeks after stroke, as were the ability to perform finger extension and the Fugl-Meyer Motor Assessment of the upper extremity (FMA_UE). These three determinants were related to the FMA_UE at 26 weeks after stroke (FMA_UE26), both directly, and via the proportional recovery prediction model. The relation between amplitude of the motor evoked potentials and FMA_UE26 was evaluated for EDC. For comparison, also the MEP amplitudes of biceps brachii and adductor digiti minimi muscles were recorded. RESULTS: Patients' ability to voluntarily extend the fingers was strongly related to FMA_UE26, in our cohort there were no false negative results for this predictor. Our data revealed that the relation between amplitude of motor evoked potential of EDC and FMA_UE26 was significant, but moderate (rs = 0.58) without added clinical value. The other tested muscles did not correlate significantly to FMA_UE26. CONCLUSIONS: Our study demonstrates no additional value of motor evoked potential amplitude of the affected EDC muscle to the clinical test of finger extension, the latter being more strongly related to FMA_UE26.

Modeling Trans-Spinal Direct Current Stimulation in the Presence of Spinal Implants.

Trans-spinal direct current stimulation (tsDCS) is a technique considered for the treatment of corticospinal damage or dysfunction. TsDCS aims to induce functional modulation in the corticospinal circuitry via a direct current (DC) generated an electric field (EF). To ensure subject safety, subjects with metallic implants are generally excluded from receiving neural dc stimulation. However, spinal injuries often require spinal implants for stabilization. Our goal was to investigate implant imposed changes to EF and current density (CD) magnitude during tsDCS. We simulated the EF and CD, generated by tsDCS in the presence of spinal rods for two electrode configurations and four implant locations along the spinal cord. For each scenario, a no-implant condition was computed for comparison. We assessed changes in EF and CD at the implant location and the EF inside the spinal cord. Our results show that implant presence was able to influence peak CD, compared to the no-implant condition. Nonetheless, the highest calculated CD levels were a factor six lower than those thought to lead to hazardous tissue-damaging effects. Additionally, implant presence did not considerably affect the average EF inside the spinal cord. Our findings do therefore not indicate potentially unsafe CD levels, or significant alterations to stimulation intensity inside the spinal cord, caused by a spinal implant during tsDCS. Our results are relevant to the safety of transcutaneous spinal stimulation applied in the presence of metallic spinal implants.

Repeatability and reliability of muscle relaxation properties induced by motor cortical stimulation.

Impaired muscle relaxation is a feature of many neuromuscular disorders. However, few tests are available to quantify muscle relaxation. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly inhibiting corticospinal drive. The aim of our study was to investigate whether repeatability and reliability of TMS-induced relaxation are greater than voluntary relaxation. Furthermore, effects of sex, cooling, and fatigue on muscle relaxation properties were studied. Muscle relaxation of deep finger flexors was assessed in 25 healthy subjects (14 men and 11 women, age 39.1 ± 12.7 and 45.3 ± 8.7 yr, respectively) with handgrip dynamometry. All outcome measures showed greater repeatability and reliability in TMS-induced relaxation compared with voluntary relaxation. The within-subject coefficient of variability of normalized peak relaxation rate was lower in TMS-induced relaxation than in voluntary relaxation (3.0% vs. 19.7% in men and 6.1% vs. 14.3% in women). The repeatability coefficient was lower (1.3 vs. 6.1 s-1 in men and 2.3 vs. 3.1 s-1 in women) and the intraclass correlation coefficient was higher (0.95 vs. 0.53 in men and 0.78 vs. 0.69 in women) for TMS-induced relaxation compared with voluntary relaxation. TMS enabled demonstration of slowing effects of sex, muscle cooling, and muscle fatigue on relaxation properties that voluntary relaxation could not. In conclusion, repeatability and reliability of TMS-induced muscle relaxation were greater compared with voluntary muscle relaxation. TMS-induced muscle relaxation has the potential to be used in clinical practice for diagnostic purposes and therapy effect monitoring in patients with impaired muscle relaxation. NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation demonstrates greater repeatability and reliability compared with voluntary relaxation, represented by the ability to demonstrate typical effects of sex, cooling, and fatigue on muscle relaxation properties that were not seen in voluntary relaxation. In clinical practice, TMS-induced muscle relaxation could be used for diagnostic purposes and therapy effect monitoring. Furthermore, fewer subjects will be needed for future studies when using TMS to demonstrate differences in muscle relaxation properties.

Modeling trans-spinal direct current stimulation for the modulation of the lumbar spinal motor pathways.

OBJECTIVE: Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects. We seek to understand the acute effect of tsDCS, including the generated electric field (EF) and its polarization effect on the spinal circuits, to determine a cellular target. We further ask how these findings can be interpreted to explain published experimental results. APPROACH: We use a realistic full body finite element volume conductor model to calculate the EF of a 2.5 mA direct current for three different electrode configurations. We apply the calculated electric field to realistic motoneuron models to investigate static changes in membrane resting potential. The results are combined with existing knowledge about the theoretical effect on a neuronal level and implemented into an existing lumbar spinal network model to simulate the resulting changes on a network level. MAIN RESULTS: Across electrode configurations, the maximum EF inside the spinal cord ranged from 0.47 V m-1 to 0.82 V m-1. Axon terminal polarization was identified to be the dominant cellular target. Also, differences in electrode placement have a large influence on axon terminal polarization. Comparison between the simulated acute effects and the electrophysiological long-term changes observed in human tsDCS studies suggest an inverse relationship between the two. SIGNIFICANCE: We provide methods and knowledge for better understanding the effects of tsDCS and serve as a basis for a more targeted and optimized application of tsDCS.

Generalization and transfer of contextual cues in motor learning.

We continuously adapt our movements in daily life, forming new internal models whenever necessary and updating existing ones. Recent work has suggested that this flexibility is enabled via sensorimotor cues, serving to access the correct internal model whenever necessary and keeping new models apart from previous ones. While research to date has mainly focused on identifying the nature of such cue representations, here we investigated whether and how these cue representations generalize, interfere, and transfer within and across effector systems. Subjects were trained to make two-stage reaching movements: a premovement that served as a cue, followed by a targeted movement that was perturbed by one of two opposite curl force fields. The direction of the premovement was uniquely coupled to the direction of the ensuing force field, enabling simultaneous learning of the two respective internal models. After training, generalization of the two premovement cues' representations was tested at untrained premovement directions, within both the trained and untrained hand. We show that the individual premovement representations generalize in a Gaussian-like pattern around the trained premovement direction. When the force fields are of unequal strengths, the cue-dependent generalization skews toward the strongest field. Furthermore, generalization patterns transfer to the nontrained hand, in an extrinsic reference frame. We conclude that contextual cues do not serve as discrete switches between multiple internal models. Instead, their generalization suggests a weighted contribution of the associated internal models based on the angular separation from the trained cues to the net motor output.

Can forearm muscle activity be selectively recorded using conventional surface EMG-electrodes in transcranial magnetic stimulation? A feasibility study.

OBJECTIVES: This feasibility study evaluates the effect of varying the position of conventional surface EMG-electrodes on the forearm when using Transcranial Magnetic Stimulation (TMS). The aim was to find optimal bipolar electrode positions for forearm extensor muscles, which would be clinically relevant to predict motor recovery after stroke. METHODS: In a healthy female subject, three rings of surface EMG-electrodes were placed around the dominant forearm, leading to 200 different electrode pairs. Both peripheral electrical stimulation and TMS were applied at suprathreshold intensities. RESULTS: With electrical stimulation of the median and radial nerve, similar waveform morphology was found for all electrode pairs, covering both flexors and extensors. Also with TMS, remarkable similarities between all electrode pairs were found, suggesting minimal selectivity. In both peripheral electrical stimulation and TMS, the curves became more irregular with decreasing inter-electrode distances. CONCLUSION: Neither with peripheral electrical stimulation nor with TMS it was possible to selectively record extensor or flexor forearm muscle activity using conventional surface EMG-electrodes. SIGNIFICANCE: Despite this negative result, the important role of the forearm extensor muscles in the prognosis of motor recovery after stroke warrants further research into novel methods for selectively recording muscle activity in TMS other than by conventional surface EMG.

Investigation of tDCS volume conduction effects in a highly realistic head model.

OBJECTIVE: We investigate volume conduction effects in transcranial direct current stimulation (tDCS) and present a guideline for efficient and yet accurate volume conductor modeling in tDCS using our newly-developed finite element (FE) approach. APPROACH: We developed a new, accurate and fast isoparametric FE approach for high-resolution geometry-adapted hexahedral meshes and tissue anisotropy. To attain a deeper insight into tDCS, we performed computer simulations, starting with a homogenized three-compartment head model and extending this step by step to a six-compartment anisotropic model. MAIN RESULTS: We are able to demonstrate important tDCS effects. First, we find channeling effects of the skin, the skull spongiosa and the cerebrospinal fluid compartments. Second, current vectors tend to be oriented towards the closest higher conducting region. Third, anisotropic WM conductivity causes current flow in directions more parallel to the WM fiber tracts. Fourth, the highest cortical current magnitudes are not only found close to the stimulation sites. Fifth, the median brain current density decreases with increasing distance from the electrodes. SIGNIFICANCE: Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

The influence of sulcus width on simulated electric fields induced by transcranial magnetic stimulation.

Volume conduction models can help in acquiring knowledge about the distribution of the electric field induced by transcranial magnetic stimulation. One aspect of a detailed model is an accurate description of the cortical surface geometry. Since its estimation is difficult, it is important to know how accurate the geometry has to be represented. Previous studies only looked at the differences caused by neglecting the complete boundary between cerebrospinal fluid (CSF) and grey matter (Thielscher et al 2011 NeuroImage 54 234-43, Bijsterbosch et al 2012 Med. Biol. Eng. Comput. 50 671-81), or by resizing the whole brain (Wagner et al 2008 Exp. Brain Res. 186 539-50). However, due to the high conductive properties of the CSF, it can be expected that alterations in sulcus width can already have a significant effect on the distribution of the electric field. To answer this question, the sulcus width of a highly realistic head model, based on T1-, T2- and diffusion-weighted magnetic resonance images, was altered systematically. This study shows that alterations in the sulcus width do not cause large differences in the majority of the electric field values. However, considerable overestimation of sulcus width produces an overestimation of the calculated field strength, also at locations distant from the target location.

Unchanged muscle fiber conduction velocity relates to mild acidosis during exhaustive bicycling.

Muscle fiber conduction velocity (MFCV) has often been shown to decrease during standardized fatiguing isometric contractions. However, several studies have indicated that the MFCV may remain constant during fatiguing dynamic exercise. It was investigated if these observations can be related to the absence of a large decrease in pH and if MFCV can be considered as a good indicator of acidosis, also during dynamic bicycle exercise. High-density surface electromyography (HDsEMG) was combined with read-outs of muscle energetics recorded by in vivo (31)P magnetic resonance spectroscopy (MRS). Measurements were performed during serial exhausting bouts of bicycle exercise at three different workloads. The HDsEMG recordings revealed a small and incoherent variation of MFCV during all high-intensity exercise bouts. (31)P MRS spectra revealed a moderate decrease in pH at the end of exercise (~0.3 units down to 6.8) and a rapid ancillary drop to pH 6.5 during recovery 30 s post-exercise. This additional degree of acidification caused a significant decrease in MFCV during cycling immediately after the rest period. From the data a significant correlation between MFCV and [H(+)] ([H(+)] = 10(-pH)) was calculated (p < 0.001, Pearson's R = -0.87). Our results confirmed the previous observations of MFCV remaining constant during fatiguing dynamic exercise. A constant MFCV is in line with a low degree of acidification, considering the presence of a correlation between pH and MFCV after further increasing acidification.

The 2nd Berlin BedRest Study: protocol and implementation.

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p < .0001), though similarly in all groups (p > or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed.

Age-related changes in motor unit number estimates in adult patients with Charcot-Marie-Tooth type 1A.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is known as a demyelinating hereditary neuropathy. Secondary axonal dysfunction is the most important determinant of disease severity. In adult patients, clinical progression may be because of further axonal deterioration as was shown with compound muscle action potential (CMAP) amplitude reductions over time. The motor unit number estimation (MUNE) technique may be more accurate to determine the number of axons as it is not disturbed by the effect of reinnervation. The purpose of this study was to investigate the number and size of motor units in relation to age in patients and controls. METHODS: In a cross-sectional design, we assessed arm and hand strength and performed electrophysiological examinations, including CMAP amplitudes and MUNE of the thenar muscles using high-density surface EMG in 69 adult patients with CMT1A and 55 age-matched healthy controls. RESULTS: In patients, lower CMAP amplitudes and MUNE values were related to hand weakness. The CMAP amplitude and MUNE value of the thenar muscles were significantly lower in patients than in controls. CMAP amplitudes declined with age in controls, but not in patients. MUNE values declined with age in both patients and controls. CONCLUSIONS: The age-dependent decrease in the number of motor units was not significantly different between patients with CMT1A and controls, indicating that loss of motor units in adult patients is limited.

Size does matter: the influence of motor unit potential size on statistical motor unit number estimates in healthy subjects.

OBJECTIVE: The statistical method of motor unit number estimation (MUNE) assumes that all motor unit potentials (MUPs) have the same size. The present study aims to evaluate the consequences of this assumption as well as its implications for the validity of statistical MUNEs. METHODS: We performed statistical and multiple point stimulation (MPS) MUNE with an array of 120 electrodes on the thenar muscles of 15 healthy subjects. These recordings allow isolation and quantification of the effect of non-uniform MUP size on MUNE, because the differences in submaximal CMAP size (and, hence, in MUNE) between electrodes are due almost entirely to differences in (summed) MUP size. RESULTS: We found no correlation between statistical and MPS MUNEs. Statistical MUNEs proved very sensitive to small variations in the "bandwidth" (variance) of the response series; MUNEs from electrodes only 8mm apart could deviate by as much as 60%. This variation in bandwidth resulted from spatial (and, hence, size) differences between the contributing MUPs. CONCLUSIONS: Statistical MUNEs are very sensitive to violation of the uniform MUP-size assumption, to an extent that blurs any correlation with MPS MUNE in healthy subjects. SIGNIFICANCE: Statistical MUNE cannot be used to detect mild to moderate motor unit losses.

Evidence of potential averaging over the finite surface of a bioelectric surface electrode.

Most bioelectric signals are not only functions of time but also exhibit a variation in spatial distribution. Surface EMG signals are often "summarized" by a large electrode. The effect of such an electrode is interpreted as averaging the potential at the surface of the skin beneath the electrode. We first introduce an electrical equivalent model to delineate this principle of averaging. Next, in a realistic finite element model of EMG generation, two outcome variables are evaluated to assess the validity of the averaging principle. One is the change in voltage distribution in the volume conductor after electrode application. The other is the change in voltage across the high impedance double layer between tissue and electrode. We found that the principle of averaging is valid, once the impedance of the double layer is sufficiently high. The simulations also revealed that skin conductivity plays a role. High-density surface EMG provided experimental evidence consistent with the simulation results. A grid with 120 small electrodes was placed over the thenar muscles of the hand. Electrical nerve stimulation assured a reproducible compound muscle response. The averaged grid response was compared with a single electrode matching the surface of the high-density electrodes. The experimental results showed relatively small errors indicating that averaging of the surface potential by the electrode is a valid principle under most practical conditions.

Heterogeneity of muscle activation in relation to force direction: a multi-channel surface electromyography study on the triceps surae muscle.

Several skeletal muscles can be divided into sub-modules, called neuromuscular compartments (NMCs), which are thought to be controlled independently and to have distinct biomechanical functions. We looked for distinct muscle activation patterns in the triceps surae muscle (TS) using surface electromyography (EMG) during voluntary contraction. Nine subjects performed isometric and isotonic plantar flexions combined with forces along pre-defined directions. Besides the forces under the ball of the foot, multi-channel surface EMG was measured with electrodes homogeneously distributed over the entire TS. Using principal component analysis, common (global) components were omitted from the EMG signals, thereby estimating muscle activity sufficiently accurate to track fine fluctuations of force during an isotonic contraction (r=0.80+/-0.09). A subsequent cluster analysis showed a topographical organization of co-activated parts of the muscle that was different between subjects. Low and negative correlations between the EMG activity within clusters were found, indicating a substantial heterogeneity of TS activation. The correlations between cluster time series and forces at the foot in specific directions differed substantially between clusters, showing that the differentially activated parts of the TS had specific biomechanical functions.

High-density surface EMG study on the time course of central nervous and peripheral neuromuscular changes during 8 weeks of bed rest with or without resistive vibration exercise.

The aim of the present study was to assess the time course and the origin of adaptations in neuromuscular function as a consequence of prolonged bed rest with or without countermeasure. Twenty healthy males volunteered to participate in the present study and were randomly assigned to either an inactive control group (Ctrl) or to a resistive vibration exercise (RVE) group. Prior to, and seven times during bed rest, we recorded high-density surface electromyogram (sEMG) signals from the vastus lateralis muscle during isometric knee extension exercise at a range of contraction intensities (5-100% of maximal voluntary isometric torque). The high-density sEMG signals were analyzed for amplitude (root mean square, RMS), frequency content (median frequency, F(med)) and muscle fiber conduction velocity (MFCV) in an attempt to describe bed rest-induced changes in neural activation properties at the levels of the motor control and muscle fibers. Without countermeasures, bed rest resulted in a significant progressive decline in maximal isometric knee extension strength, whereas RMS remained unaltered throughout the bed rest period. In line with observed muscle atrophy, both F(med) and MFCV declined during bed rest. RVE training during bed rest resulted in maintained maximal isometric knee extension strength, and a strong increase ( approximately 30%) in maximal EMG amplitude, from 10 days of bed rest on. Exclusion of other factors led to the conclusion that the RVE training increased motor unit firing rates as a consequence of an increased excitability of motor neurons. An increased firing rate might have been essential under training sessions, but it did not affect isometric voluntary torque capacity.

Characteristics of fast voluntary and electrically evoked isometric knee extensions during 56 days of bed rest with and without exercise countermeasure.

The contractile characteristics of fast voluntary and electrically evoked unilateral isometric knee extensions were followed in 16 healthy men during 56 days of horizontal bed rest and assessed at bed rest days 4, 7, 10, 17, 24, 38 and 56. Subjects were randomized to either an inactive control group (Ctrl, n = 8) or a resistive vibration exercise countermeasure group (RVE, n = 8). No changes were observed in neural activation, indicated by the amplitude of the surface electromyogram, or the initial rate of voluntary torque development in either group during bed rest. In contrast, for Ctrl, the force oscillation amplitude at 10 Hz stimulation increased by 48% (P < 0.01), the time to reach peak torque at 300 Hz stimulation decreased by 7% (P < 0.01), and the half relaxation time at 150 Hz stimulation tended to be slightly reduced by 3% (P = 0.056) after 56 days of bed rest. No changes were observed for RVE. Torque production at 10 Hz stimulation relative to maximal (150 Hz) stimulation was increased after bed rest for both Ctrl (15%; P < 0.05) and RVE (41%; P < 0.05). In conclusion, bed rest without exercise countermeasure resulted in intrinsic speed properties of a faster knee extensor group, which may have partly contributed to the preserved ability to perform fast voluntary contractions. The changes in intrinsic contractile properties were prevented by resistive vibration exercise, and voluntary motor performance remained unaltered for RVE subjects as well.

Highly demanding resistive vibration exercise program is tolerated during 56 days of strict bed-rest.

Several studies have tried to find countermeasures against musculoskeletal de-conditioning during bed-rest, but none of them yielded decisive results. We hypothesised that resistive vibration exercise (RVE) might be a suitable training modality. We have therefore carried out a bed-rest study to evaluate its feasibility and efficacy during 56 days of bed-rest. Twenty healthy male volunteers aged 24 to 43 years were recruited and, after medical check-ups, randomised to a non-exercising control (Ctrl) group or a group that performed RVE 11 times per week. Strict bed-rest was controlled by video surveillance. The diet was controlled. RVE was performed in supine position, with a static force component of about twice the body weight and a smaller dynamic force component. RVE comprised four different units (squats, heel raises, toe raises, kicks), each of which lasted 60 - 100 seconds. Pre and post exercise levels of lactate were measured once weekly. Body weight was measured daily on a bed scale. Pain questionnaires were obtained in regular intervals during and after the bed-rest. Vibration frequency was set to 19 Hz at the beginning and progressed to 25.9 Hz (SD 1.9) at the end of the study, suggesting that the dynamic force component increased by 90 %. The maximum sustainable exercise time for squat exercise increased from 86 s (SD 21) on day 11 of the BR to 176 s (SD 73) on day 53 (p = 0.006). On the same days, post-exercise lactate levels increased from 6.9 mmol/l (SD2.3) to 9.2 mmol/l (SD 3.5, p = 0.01). On average, body weight was unchanged in both groups during bed-rest, but single individuals in both groups depicted significant weight changes ranging from - 10 % to + 10 % (p < 0.001). Lower limb pain was more frequent during bed-rest in the RVE subjects than in Ctrl (p = 0.035). During early recovery, subjects of both groups suffered from muscle pain to a comparable extent, but foot pain was more common in Ctrl than in RVE (p = 0.013 for plantar pain, p = 0.074 for dorsal foot pain). Our results indicate that RVE is feasible twice daily during bed-rest in young healthy males, provided that one afternoon and one entire day per week are free. Exercise progression, mainly by progression of vibration frequency, yielded increases in maximum sustainable exercise time and blood lactate. In conclusion, RVE as performed in this study, appears to be safe.

Strength, size and activation of knee extensors followed during 8 weeks of horizontal bed rest and the influence of a countermeasure.

Changes in the quadriceps femoris muscle with respect to anatomical cross sectional area (CSA), neural activation level and muscle strength were determined in 18 healthy men subjected to 8 weeks of horizontal bed rest (BR) with (n = 9) and without (n = 9) resistive vibration exercise (RVE). CSA of the knee extensor muscle group was measured with magnetic resonance imaging every 2 weeks during bed rest. In the control subjects (Ctrl), quadriceps femoris CSA decreased linearly over the 8 weeks of bed rest to -14.1 +/- 5.2% (P < 0.05). This reduction was significantly (P < 0.001) mitigated by the exercise paradigm (-3.5 +/- 4.2%; P < 0.05). Prior to and seven times during bed rest, maximal unilateral voluntary torque (MVT) values of the right leg were measured together with neural activation levels by means of a superimposed stimulation technique. For Ctrl, MVT decreased also linearly over time to -16.8 +/- 7.4% after 8 weeks of bed rest (P < 0.01), whereas the exercise paradigm fully maintained MVT during bed rest. In contrast to previous reports, the maximal voluntary activation remained unaltered for both groups throughout the study. For Ctrl, the absence of deterioration of the activation level might have been related to the repeated testing of muscle function during the bed rest. This notion was supported by the observation that for a subset of Ctrl subjects (n = 5) the MVT of the left leg, which was not tested during BR, was reduced by 20.5 +/- 10.1%, (P < 0.01) which was for those five subjects significantly (P < 0.05) more than the 11.1 +/- 9.2% (P < 0.01) reduction for the right, regularly tested leg.