Publications

2008

Clark, B. C., and T. M. Manini. 2008. “Sarcopenia =/= dynapenia”. J Gerontol A Biol Sci Med Sci 63: 829-34. https://doi.org/10.1093/gerona/63.8.829.
Maximal voluntary force (strength) production declines with age and contributes to physical dependence and mortality. Consequently, a great deal of research has focused on identifying strategies to maintain muscle mass during the aging process and elucidating key molecular pathways of atrophy, with the rationale that the loss of strength is primarily a direct result of the age-associated declines in mass (sarcopenia). However, recent evidence questions this relationship and in this Green Banana article we argue the role of sarcopenia in mediating the age-associated loss of strength (which we will coin as dynapenia) does not deserve the attention it has attracted in both the scientific literature and popular press. Rather, we propose that alternative mechanisms underlie dynapenia (i.e., alterations in contractile properties or neurologic function), and urge that greater attention be paid to these variables in determining their role in dynapenia.
Clark, B. C., L. C. Issac, J. L. Lane, L. A. Damron, and R. L. Hoffman. 2008. “Neuromuscular plasticity during and following 3 wk of human forearm cast immobilization”. J Appl Physiol (1985) 105: 868-78. https://doi.org/10.1152/japplphysiol.90530.2008.
Prolonged reductions in muscle activity results in alterations in neuromuscular properties; however, the time course of adaptations is not fully understood, and many of the specific adaptations have not been identified. This study evaluated the temporal evolution of adaptations in neuromuscular properties during and following 3 wk of immobilization. We utilized a combination of techniques involving nerve stimulation and transcranial magnetic stimulation to assess changes in central activation of muscle, along with spinal (H reflex) and corticospinal excitability [i.e., motor-evoked potential (MEP) amplitude, silent period (SP)] and contractile properties in 10 healthy humans undergoing 3 wk of forearm immobilization and 9 control subjects. Immobilization induced deficits in central activation (85 +/- 3 to 67 +/- 7% ) that returned to baseline levels 1 wk after cast removal. The flexor carpii radialis MEP amplitude increased greater than twofold after the first week of immobilization and remained elevated throughout immobilization and 1 wk after cast removal. Additionally, we observed a prolongation of the SP 1 wk after cast removal compared with baseline (78.5 +/- 7.1 to 98.2 +/- 8.7 ms). The contractile properties were also altered, since the rate of evoked force relaxation was slower following immobilization (-14.5 +/- 1.4 to -11.3 +/- 1.0% peak force/ms), and remained depressed 1 wk after cast removal (-10.5 +/- 0.8% peak force/ms). These observations detail the time course of adaptations in corticospinal and contractile properties associated with disuse and illustrate the profound effect of immobilization on the human neuromuscular system as evidenced by the alterations in corticospinal excitability persisting 1 wk following cast removal.
Clark, B. C., R. L. Hoffman, and D. W. Russ. 2008. “Immobilization-induced increase in fatigue resistance is not explained by changes in the muscle metaboreflex”. Muscle Nerve 38: 1466-73. https://doi.org/10.1002/mus.21127.
Immobilization has been reported to enhance fatigability, which is paradoxical in light of the metabolic and molecular alterations that occur in atrophied muscles. We examined whether the immobilization-induced enhancement in fatigability was associated with attenuation in the muscle metaboreflex response. Ten subjects were examined after 3 weeks of hand-forearm immobilization. The time to task failure of a handgrip contraction (20% intensity) was determined along with heart rate (HR) and mean arterial pressure (MAP) at rest, during the task and during a 2-min postexercise muscle ischemia (PEMI) test that continues to stimulate the metaboreflex. Immobilization decreased strength by 25% (P0.01) and increased the time to task failure by 21% (P=0.03). However, no changes were observed for the HR and MAP responses to the exercise task or during PEMI (P>0.05). These findings indicate that the augmentation of time to task failure with immobilization is not associated with changes in the pressor or metaboreflex responses.

2007

Monzon, A., P. F. Hemler, M. A. Nails, T. M. Manini, B. C. Clark, T. B. Harris, and M. J. McAuuliffe. 2007. “Segmentation of Magnetic Resonance Images of the Thighs for a New National Institutes of Health Initiative”. Proceedings of the Society of Photo-Optical Instrumentation Engineers (SPIE): Medical Imaging 6212: 65123L.

This paper describes a new system for semi-automatically segmenting the background, subcutaneous fat, interstitial fat, muscle, bone, and bone marrow from magnetic resonance images (MRI's) of volunteers for a new osteoarthritis study. Our system first creates separate right and left thigh images from a single MR image containing both legs. The subcutaneous fat boundary is very difficult to detect in these images and is therefore interactively defined with a single boundary. The volume within the boundary is then automatically processed with a series of clustering and morphological operations designed to identify and classify the different tissue types required for this study. Once the tissues have been identified, the volume of each tissue is determined and a single, false colored, segmented image results. We quantitatively compare the segmentation in three different ways. In our first method we simply compare the tissue volumes of the resulting segmentations performed independently on both the left and right thigh. A second quantification method compares our results temporally with three image sets of the same volunteer made one month apart including a month of leg disuse. Our final quantification methodology compares the volumes of different tissues detected with our system to the results of a manual segmentation performed by a trained expert. The segmented image results of four different volunteers using images acquired at three different times suggests that the system described in this paper provides more consistent results than the manually segmented set. Furthermore, measurements of the left and right thigh and temporal results for both segmentation methods follow the anticipated trend of increasing fat and decreasing muscle over the period of disuse.

Manini, T. M., B. C. Clark, M. A. Nalls, B. H. Goodpaster, L. L. Ploutz-Snyder, and T. B. Harris. 2007. “Reduced physical activity increases intermuscular adipose tissue in healthy young adults”. Am J Clin Nutr 85: 377-84. https://doi.org/10.1093/ajcn/85.2.377.
BACKGROUND: Recent findings suggest that higher levels of intermuscular adipose tissue (IMAT) are associated with glucose dysregulation, lower levels of muscle strength, and a heightened risk of disability. Although several studies have described adaptations in muscle after reduced physical activity, the change in IMAT in healthy young adults is unknown. OBJECTIVE: The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss. DESIGN: The subjects (6 men and 12 women aged 19-28 y) underwent a 4-wk control period, which was followed by 4 wk of unilateral lower limb suspension. Volumes of whole muscle, subcutaneous adipose tissue, and IMAT were assessed by using magnetic resonance imaging in the thigh and calf. Muscle strength was assessed during maximal voluntary isometric contractions. RESULTS: No changes were observed in the control period. Reduced physical activity decreased thigh and calf muscle volumes by 7.4% and 7.9% (P 0.001), respectively; no significant change in subcutaneous adipose tissue was observed. Additionally, IMAT increased in both regions; the increase was larger in the calf (20%) than in the thigh (14.5%) (P
Clark, B. C., T. M. Manini, and L. L. Ploutz-Snyder. 2007. “Fatigue-induced changes in phasic muscle activation patterns during dynamic trunk extension exercise”. Am J Phys Med Rehabil 86: 373-79. https://doi.org/10.1097/PHM.0b013e3180321689.
OBJECTIVE: To investigate the influence of fatigue on phasic muscle-activation patterns during dynamic trunk extension exercise. DESIGN: Fifteen healthy volunteers performed dynamic trunk-extension exercise through a 30-degree range-of-motion (ROM) exercise to task failure at an intensity of 50% of maximum. Electromyography (EMG) signals were recorded unilaterally from the lumbar extensor, gluteus maximus, and biceps femoris muscles, and signal amplitude was analyzed in 10-degree increments during the unfatigued and fatigued states (0-10 degrees from torso horizontal to the ground was considered extension, and 11-20 and 21-30 degrees of flexion relative to this were considered midphase and flexion, respectively). RESULTS: Lumbar extensor EMG was approximately 75% of maximum EMG, with no differences being observed with respect to ROM or fatigue state. The gluteus maximus demonstrated an altered phasic activation pattern with fatigue, with an increased recruitment during the extension phase (fatigued-state extension-phase EMG: 89.1 +/- 8.3% > flexion phase EMG: 37.8% +/- 9.1%). The biceps femoris demonstrated a similar response during both the fatigued and unfatigued states (fatigued-state extension EMG: 77.8 +/- 5.4% > midphase EMG: 65.8 +/- 5.7% > flexion EMG: 46.8 +/- 4.0%; unfatigued-state extension EMG: 46.1 +/- 3.7% > flexion EMG: 27.1 +/- 2.6%). CONCLUSIONS: During this exercise, as one moves from flexion to extension, hip extensor muscle activity increases, whereas lumbar extensor activity does not. Additionally, fatigue results in an altered recruitment pattern, with the hip extensors being activated to a greater extent in the extension phase. These findings suggest that when this exercise is performed in the prone position, it can be used to stimulate the lumbar and hip extensor muscles, but the specific exercise protocol in terms of set/repetition number and ROM will influence which muscles are primarily targeted.
Cook, S. B., B. C. Clark, and L. L. Ploutz-Snyder. 2007. “Effects of exercise load and blood-flow restriction on skeletal muscle function”. Med Sci Sports Exerc 39: 1708-13. https://doi.org/10.1249/mss.0b013e31812383d6.
Resistance training at low loads with blood flow restriction (BFR) (also known as Kaatsu) has been shown to stimulate increases in muscle size and strength. It is unclear how occlusion pressure, exercise intensity, and occlusion duration interact, or which combination of these factors results in the most potent muscle stimulus. PURPOSE: To determine the effect of eight BFR protocols on muscle fatigue (decrement in maximal voluntary contraction (MVC) after the performance of exercise), and to compare the decrement in MVC with the currently recommended resistance exercise intensity ( 80% MVC). METHODS: During five test sessions, 21 subjects (14 males and 7 females, 27.7 +/- 4.9 yr) completed nine protocols, each consisting of three sets of knee extensions (KE) to failure. One protocol was high-load (HL) exercise (80% MVC) with no BFR, and the other eight were BFR at varying levels of contraction intensity (20 or 40% MVC), occlusion pressure (partial ( 160 mm Hg) or complete ( 300 mm Hg)), and occlusion duration (off during the rest between sets or continuously applied). To evaluate each protocol, MVC were performed before and after exercise, and the decrement in force was calculated. RESULTS: Three sets of KE at 20% MVC with continuous partial occlusion (20%(ConPar)) resulted in a greater decrement in MVC compared with HL (31 vs 19%, P = 0.001). None of the other BFR protocols were different from the HL protocol, nor were they different from 20%(ConPar) (P > 0.05). CONCLUSION: All BFR protocols elicited at least as much fatigue as HL, even though lower loads were used. The 20%(ConPar) protocol was the only one that elicited significantly more fatigue than HL. Future research should evaluate protocol training effectiveness and overall safety of BFR exercise.
Clark, B. C., J. R. Pierce, T. M. Manini, and L. L. Ploutz-Snyder. 2007. “Effect of prolonged unweighting of human skeletal muscle on neuromotor force control”. Eur J Appl Physiol 100: 53-62. https://doi.org/10.1007/s00421-007-0399-6.
The purpose of this study was to determine the effect of 4 weeks of unilateral lower limb suspension (ULLS) on the fluctuations in motor output and the associated physiological changes. Subjects (n = 17) performed steady isometric plantarflexion (PF) and knee extension (KE) tasks, and KE shortening and lengthening contractions (intensity = 25% maximum). Spinal excitability of the soleus muscle was assessed via the H-reflex, muscle cross-sectional area (CSA) via MRI, along with EMG activity during the PF tasks. Following ULLS, isometric force fluctuations increased approximately 12% for the PF, and 22% for the KE (P 0.05), with no difference in the pattern of PF muscle activation (P = 0.46). The unsteadiness of lengthening KE contractions increased 25% following ULLS (P = 0.03), while KE steadiness during shortening contractions was not altered (P = 0.98). Significant correlations were observed between the percent changes in PF isometric force fluctuations and H-reflex (r = 0.49, P = 0.04), and between the PF isometric force fluctuations and PF CSA (r = -0.61, P 0.01). These findings suggest the effects of unweighting on neuromotor performance are muscle group and contraction type dependent, and that the disuse-paradigm altering muscle CSA and spinal excitability may serve to mediate the associated loss of steadiness.
Clark, B. C., S. B. Cook, and L. L. Ploutz-Snyder. 2007. “Reliability of techniques to assess human neuromuscular function in vivo”. J Electromyogr Kinesiol 17: 90-101. https://doi.org/10.1016/j.jelekin.2005.11.008.
The purpose of this study was to comprehensively evaluate the reliability of a large number of commonly utilized experimental tests of in vivo human neuromuscular function separated by 4-weeks. Numerous electrophysiological parameters (i.e., voluntary and evoked electromyogram [EMG] signals), contractile properties (i.e., evoked forces and rates of force development and relaxation), muscle morphology (i.e., MRI-derived cross-sectional area [CSA]) and performance tasks (i.e., steadiness and time to task failure) were assessed from the plantarflexor muscle group in 17 subjects before and following 4-weeks where they maintained their normal lifestyle. The reliability of the measured variables had wide-ranging levels of consistency, with coefficient of variations (CV) ranging from approximately 2% to 20%, and intraclass correlation coefficients (ICC) between 0.53 and 0.99. Overall, we observed moderate to high-levels of reliability in the vast majority of the variables we assessed (24 out of the 29 had ICC>0.70 and CV15%). The variables demonstrating the highest reliability were: CSA (ICC=0.93-0.98), strength (ICC=0.97), an index of nerve conduction velocity (ICC=0.95), and H-reflex amplitude (ICC=0.93). Conversely, the variables demonstrating the lowest reliability were: the amplitude of voluntary EMG signal (ICC=0.53-0.88), and the time to task failure of a sustained submaximal contraction (ICC=0.64). Additionally, relatively little systematic bias (calculated through the limits of agreement) was observed in these measures over the repeat sessions. In conclusion, while the reliability differed between the various measures, in general it was rather high even when the testing sessions are separated by a relatively long duration of time.

2006