Daniel L. Belavý

Magnetic resonance imaging assessment of trunk muscles during prolonged bed rest

Study Design. Prospective longitudinal study. Objective. To investigate, using magnetic resonance imaging (MRI), the influence of bed rest on the lumbopelvic musculature. Summary of Background Data. Reduced gravitational loading and inactivity (bed rest) are known to result in significant change in musculoskeletal function, although little is known about its effects on specific muscles of the lumbopelvic region. Methods. Ten healthy male subjects underwent 8 weeks of bed rest with 6 months of follow-up. MRI of the lumbopelvic region was conducted at regular time-points during and after bed rest. Using uniplanar images at L4, cross-sectional areas (CSAs) of the multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral abdominal, and rectus abdominis muscles were measured. Results. Multifidus CSA decreased by day 14 of bed rest (F = 7.4, P = 0.04). The lumbar erector spinae and quadratus lumborum CSA showed no statistically significant difference to baseline across the time of bed rest (P > 0.05). The anterolateral abdominal, rectus abdominis, and psoas CSA all increased over this time. Psoas CSA increased by day 14 (F = 6.9, P = 0.047) and remained so until day 56, whereas the anterolateral abdominal CSA (F = 29.4, P = 0.003) and rectus abdominis CSA (F = 8.9, P = 0.03) were not statistically larger than baseline until day 56. On reambulation after completion of the bed rest phase, multifidus, anterolateral abdominal, and rectus abdominis CSA returned to baseline levels (P > 0.05) by day 4 of follow-up, whereas psoas CSA returned to baseline level after day 28 of the follow-up period. Conclusions. Bed rest resulted in selective atrophy of the multifidus muscle. An increased CSA of the trunk flexor musculature (increases in psoas, anterolateral abdominal, and rectus abdominis muscles) may reflect muscle shortening or possible overactivity during bed rest. Some of the changes resemble those seen in low back pain and may in part explain the negative effects of bed rest seen in low back pain sufferers.

Countermeasures against lumbar spine deconditioning in prolonged bed rest: resistive exercise with and without whole body vibration

To evaluate the effect of short-duration, high-load resistive exercise, with and without whole body vibration on lumbar muscle size, intervertebral disk and spinal morphology changes, and low back pain (LBP) incidence during prolonged bed rest, 24 subjects underwent 60 days of head-down tilt bed rest and performed either resistive vibration exercise (n = 7), resistive exercise only (n = 8), or no exercise (n = 9; 2nd Berlin Bed-Rest Study). Discal and spinal shape was measured from sagittal plane magnetic resonance images. Cross-sectional areas (CSAs) of the multifidus, erector spinae, quadratus lumborum, and psoas were measured on para-axial magnetic resonance images. LBP incidence was assessed with questionnaires at regular intervals. The countermeasures reduced CSA loss in the multifidus, lumbar erector spinae and quadratus lumborum muscles, with greater increases in psoas muscle CSA seen in the countermeasure groups (P ≤ 0.004). There was little statistical evidence for an additional effect of whole body vibration above resistive exercise alone on these muscle changes. Exercise subjects reported LBP more frequently in the first week of bed rest, but this was only significant in resistive exercise only (P = 0.011 vs. control, resistive vibration exercise vs. control: P = 0.56). No effect of the countermeasures on changes in spinal morphology was seen (P ≥ 0.22). The results suggest that high-load resistive exercise, with or without whole body vibration, performed 3 days/wk can reduce lumbar muscle atrophy, but further countermeasure optimization is required.

Resistive simulated weightbearing exercise with whole body vibration reduces lumbar spine deconditioning in bed-rest.

Study Design. Randomized controlled trial. Objective. Determine the effectiveness a resistive exercise countermeasure with whole-body vibration in relation to lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight (bed-rest). Summary of Background Data. Spinal lengthening, flattening of the spinal curves, increases in disc size, and muscle atrophy are commonly seen in spaceflight simulation. This may represent a risk for low back injury. Consideration of exercise countermeasures against these changes is critical for success of long-term spaceflight missions. Methods. Twenty healthy male subjects underwent 8-weeks of bed-rest with 6-months follow-up and were randomly allocated to an inactive control or countermeasure exercise group. Magnetic resonance imaging of the lumbo-pelvic region was conducted at regular time-points during and after bed-rest. Using uniplanar images at L4, cross-sectional areas of the multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral abdominal, and rectus abdominis muscles were measured. Sagittal scans were used to assess lumbar spine morphology (length, sagittal disc area and height, and intervertebral angles). Results. The countermeasure group exhibited less multifidus muscle atrophy (P = 0.024) and its atrophy did not persist long-term as in the control group (up to 3-months; P < 0.006). Spinal lengthening (P = 0.03) and increases in disc area (P = 0.041) were also reduced. Significant partial correlations (P < 0.001) existed between spinal morphology and muscle cross-sectional area changes. Conclusion. The resistive vibration exercise countermeasure reduced, but did not entirely prevent, multifidus muscle atrophy and passive spinal tissue deconditioning during bed-rest. Atrophy of the multifidus muscles was persistent long-term in the inactive subjects. Future work could consider closer attention to spinal posture during exercise and optimizing exercise dose.

Muscle Atrophy and Changes in Spinal Morphology Is the Lumbar Spine Vulnerable After Prolonged Bed-Rest?

Study Design. Prospective longitudinal study. Objective. To evaluate the effect of bed-rest on the lumbar musculature and soft-tissues. Summary of Background Data. Earlier work has suggested that the risk of low back injury is higher after overnight bed-rest or spaceflight. Changes in spinal morphology and atrophy in musculature important in stabilizing the spine could be responsible for this, but there are limited data on how the lumbar musculature and vertebral structures are affected during bed-rest. Methods. Nine male subjects underwent 60-days head-down tilt bed-rest as part of the second Berlin Bed-Rest Study. Disc volume, intervertebral spinal length, intervertebral lordosis angle, and disc height were measured on sagittal plane magnetic resonance images. Axial magnetic resonance images were used to measure cross-sectional areas (CSAs) of the multifidus (MF), erector spinae, quadratus lumborum, and psoas from L1 to L5. Subjects completed low back pain (LBP) questionnaires for the first 7-days after bed-rest. Results. Increases in disc volume, spinal length (greatest at lower lumbar spine), loss of the lower lumbar lordosis, and move to a more lordotic position at the upper lumbar spine (P < 0.0097) were seen. The CSAs of all muscles changed (P < 0.002), with the rate of atrophy greatest at L4 and L5 in MF (P < 0.002) and at L1 and L2 in the erector spinae (P = 0.0006). Atrophy of the quadratus lumborum was consistent throughout the muscle (P = 0.15), but CSA of psoas muscle increased (P < 0.0001). Subjects who reported LBP after bed-rest showed, before reambulation, greater increases in posterior disc height, and greater losses of MF CSA at L4 and L5 than subjects who did not report pain (all P < 0.085). Conclusion. These results provide evidence that changes in the lumbar discs during bed-rest and selective atrophy of the MF muscle may be important factors in the occurrence of LBP after prolonged bed-rest.

Trabecular and cortical bone density and architecture in women after 60 days of bed rest using high-resolution pQCT: WISE 2005

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse‐related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty‐four healthy women aged 25 to 40 years participated in 60 days of strict 6‐degree head‐down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high‐protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Bed rest was associated with reductions in all distal tibial density parameters (p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius (p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius (p = 0.021) and distal tibia (p < 0.001). Cortical thickness decreased at the distal tibia only (p < 0.001). There were no significant effects on bone structure or density of the countermeasures (p ≥ 0.057). As measured with HR‐pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes.

Heterogeneous atrophy occurs within individual lower limb muscles during 60 days of bed rest

To better understand disuse muscle atrophy, via magnetic resonance imaging, we sequentially measured muscle cross-sectional area along the entire length of all individual muscles from the hip to ankle in nine male subjects participating in 60-day head-down tilt bed rest (2nd Berlin BedRest Study; BBR2-2). We hypothesized that individual muscles would not atrophy uniformly along their length such that different regions of an individual muscle would atrophy to different extents. This hypothesis was confirmed for the adductor magnus, vasti, lateral hamstrings, medial hamstrings, rectus femoris, medial gastrocnemius, lateral gastrocnemius, tibialis posterior, flexor hallucis longus, flexor digitorum longus, peroneals, and tibialis anterior muscles (P ≤ 0.004). In contrast, the hypothesis was not confirmed in the soleus, adductor brevis, gracilis, pectineus, and extensor digitorum longus muscles (P ≥ 0.20). The extent of atrophy only weakly correlated (r = -0.30, P < 0.001) with the location of greatest cross-sectional area. The rate of atrophy during bed rest also differed between muscles (P < 0.0001) and between some synergists. Most muscles recovered to their baseline size between 14 and 90 days after bed rest, but flexor hallucis longus, flexor digitorum longus, and lateral gastrocnemius required longer than 90 days before recovery occurred. On the basis of findings of differential atrophy between muscles and evidence in the literature, we interpret our findings of intramuscular atrophy to reflect differential disuse of functionally different muscle regions. The current work represents the first lower-limb wide survey of intramuscular differences in disuse atrophy. We conclude that intramuscular differential atrophy occurs in most, but not all, of the muscles of the lower limb during prolonged bed rest.

WISE-2005: Bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity☆

To better understand the effects of prolonged bed-rest in women, 24 healthy women aged 25 to 40 years participated in 60-days of strict 6° head-down tilt bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8) which performed no countermeasure, an exercise group (EXE, n=8) undertaking a combination of resistive and endurance training or a nutrition group (NUT, n=8), which received a high protein diet. Using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA), bone mineral density (BMD) changes at various sites, body-composition and lower-leg and forearm muscle cross-sectional area were measured up to 1-year after bed-rest. Bone loss was greatest at the distal tibia and proximal femur, though losses in trabecular density at the distal radius were also seen. Some of these bone losses remained statistically significant one-year after bed-rest. There was no statistically significant impediment of bone loss by either countermeasure in comparison to the control-group. The exercise countermeasure did, however, reduce muscle cross-sectional area and lean mass loss in the lower-limb and also resulted in a greater loss of fat mass whereas the nutrition countermeasure had no impact on these parameters. The findings suggest that regional differences in bone loss occur in women during prolonged bed-rest with incomplete recovery of this loss one-year after bed-rest. The countermeasures as implemented were not optimal in preventing bone loss during bed-rest and further development is required.

Changes in intervertebral disc morphology persist 5 mo after 21-day bed rest

As part of the nutrition-countermeasures (NUC) study in Cologne, Germany in 2010, seven healthy male subjects underwent 21 days of head-down tilt bed rest and returned 153 days later to undergo a second bout of 21-day bed rest. As part of this model, we aimed to examine the recovery of the lumbar intervertebral discs and muscle cross-sectional area (CSA) after bed rest using magnetic resonance imaging and conduct a pilot study on the effects of bed rest in lumbar muscle activation, as measured by signal intensity changes in T(2)-weighted images after a standardized isometric spinal extension loading task. The changes in intervertebral disc volume, anterior and posterior disc height, and intervertebral length seen after bed rest did not return to prebed-rest values 153 days later. While recovery of muscle CSA occurred after bed rest, increases (P ≤ 0.016) in multifidus, psoas, and quadratus lumborum muscle CSA were seen 153 days after bed rest. A trend was seen for greater activation of the erector spinae and multifidus muscles in the standardized loading task after bed rest. Greater reductions of multifidus and psoas CSA muscle and greater increases in multifidus signal intensity with loading were associated with incidence of low back pain in the first 28 days after bed rest (P ≤ 0.044). The current study contributes to our understanding of the recovery of the lumbar spine after 21-day bed rest, and the main finding was that a decrease in spinal extensor muscle CSA recovers within 5 mo after bed rest but that changes in the intervertebral discs persist.

Bed rest and cognition: effects on executive functioning and reaction time

INTRODUCTION Executive functions are high-order aspects of cognition heavily dependent upon the prefrontal cortex. Both prefrontal cortex activity and executive function task performance are enhanced by participation in aerobic physical activity, suggesting that a lack of such activity during the bed rest model of prolonged weightlessness might induce executive function deficits. METHODS Twenty-four healthy males (ages 21-45 yr) undertook 60 d of head-down bed rest (-6 degrees) for the 2nd Berlin Bed Rest Study (BBR2-2). Three executive function tasks (Iowa Gambling Task, working memory, and flanker) and a reaction time task were administered before, during, and after bed rest. RESULTS Iowa Gambling Task scores were significantly worse during bed rest (1.7 +/- 6.9) than in other sessions (24.3 +/- 7.8). Effects on working memory and flanker task performance were less obvious, requiring practice effects to be considered. Reaction time was significantly slower after bed rest (569 +/- 42 ms) than in earlier tests (529 +/- 45 ms). There was also significantly less intrasubject variability in reaction time after bed rest, consistent with more efficient executive functioning at this stage. DISCUSSION Our results provide some evidence for a detrimental effect of bed rest on executive functioning. Whether this stems from a lack of aerobic physical activity and/or changes in the prefrontal cortex remains to be determined. Cognitive effects of bed rest could have implications for the planned human exploration of Mars, and for medical and lifestyle conditions with inadequate levels of aerobic physical activity.

Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise

Protein calcium sensors of the Homer family have been proposed to modulate the activity of various ion channels and nuclear factor of activated T cells (NFAT), the transcription factor modulating skeletal muscle differentiation. We monitored Homer expression and subcellular localization in human skeletal muscle biopsies following 60 d of bedrest [Second Berlin Bedrest Study (BBR2‐2)]. Soleus (SOL) and vastus lateralis (VL) biopsies were taken at start (pre) and at end (end) of bedrest from healthy male volunteers of a control group without exercise (CTR; n=9), a resistive‐only exercise group (RE; n=7), and a combined resistive/vibration exercise group (RVE; n=7). Confocal analysis showed Homer immunoreactivity at the postsynaptic microdomain of the neuromuscular junction (NMJ) at bedrest start. After bedrest, Homer immunoreactivity decreased (CTR), remained unchanged (RE), or increased (RVE) at the NMJ. Homer2 mRNA and protein were differently regulated in a muscle‐specific way. Activated NFATc1 translocates from cytoplasm to nucleus; increased amounts of NFATc1‐immunopositive slow‐type myonuclei were found in RVE myofibers of both muscles. Pulldown assays identified NFATc1 and Homer as molecular partners in skeletal muscle. A direct motor nerve control of Homer2 was confirmed in rat NMJs by in vivo denervation. Homer2 is localized at the NMJ and is part of the calcineurin‐NFATc1 signaling pathway. RVE has additional benefit over RE as countermeasure preventing disuse‐induced neuromuscular maladaptation during bedrest.—Salanova, M., Bortoloso, E., Schiffl, G., Gutsmann, M., Belavý, D. L., Felsenberg, D., Furlan, S., Volpe, P., Blottner, D. Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise. FASEB J. 25, 4312–4325 (2011). www.fasebj.org