Publications

2009

Umbel, J. D., R. L. Hoffman, D. J. Dearth, G. S. Chleboun, T. M. Manini, and B. C. Clark. 2009. “Delayed-Onset Muscle Soreness Induced by Low-Load Blood Flow-Restricted Exercise”. Eur J Appl Physiol 107: 687-95. https://doi.org/10.1007/s00421-009-1175-6.
We performed two experiments to describe the magnitude of delayed-onset muscle soreness (DOMS) associated with blood flow restriction (BFR) exercise and to determine the contribution of the concentric (CON) versus eccentric (ECC) actions of BFR exercise on DOMS. In experiment 1, nine subjects performed three sets of unilateral knee extension BFR exercise at 35% of maximal voluntary contraction (MVC) to failure with a thigh cuff inflated 30% above brachial systolic pressure. Subjects repeated the protocol with the contralateral limb without flow restriction. Resting soreness (0-10 scale) and algometry (pain-pressure threshold; PPT) were assessed before and 24, 48 and 96 h post-exercise. Additionally, MVC and vastus lateralis cross-sectional area (CSA) were measured as indices of exercise-induced muscle damage. At 24-h post-exercise, BFR exercise resulted in more soreness than exercise without BFR (2.8 +/- 0.3 vs 1.7 +/- 0.5) and greater reductions in PPT (15.2 +/- 1.7 vs. 20 +/- 2.3 N) and MVC (14.1 +/- 2.5% decrease vs. 1.5 +/- 4.5% decrease) (p
Clark, B. C., S. Walkowski, R. R. Conatser, D. C. Eland, and J. N. Howell. 2009. “Muscle Functional Magnetic Resonance Imaging and Acute Low Back Pain: A Pilot Study to Characterize Lumbar Muscle Activity Asymmetries and Examine the Effects of Osteopathic Manipulative Treatment”. Osteopath Med Prim Care 3: 7. https://doi.org/10.1186/1750-4732-3-7.
BACKGROUND: Muscle functional magnetic resonance imaging (mfMRI) measures transverse relaxation time (T2), and allows for determination of the spatial pattern of muscle activation. The purposes of this pilot study were to examine whether MRI-derived T2 or side-to-side differences in T2 (asymmetries) differ in low back muscles between subjects with acute low back pain (LBP) compared to asymptomatic controls, and to determine if a single osteopathic manipulative treatment (OMT) session alters these T2 properties immediately and 48-hours after treatment. METHODS: Subjects with non-specific acute LBP (mean score on 110 visual analog score = 3.02 +/- 2.81) and asymptomatic controls (n = 9/group) underwent an MRI, and subsequently the LBP subjects received OMT and then underwent another MRI. The LBP subjects reported back for an additional MRI 48-hours following their initial visit. T2 and T2 asymmetry were calculated from regions of interest for the psoas, quadratus lumborum (QL), multifidus, and iliocostalis lumborum/longissimus thoracis (IL/LT) muscles. RESULTS: No differences were observed between the groups when T2 was averaged for the left and right side muscles. However, the QL displayed a significantly greater T2 asymmetry in LBP subjects when compared to controls (29.1 +/- 4.3 vs. 15.9 +/- 4.1%; p = 0.05). The psoas muscle also displayed a relatively large, albeit non-significant, mean difference (22.7 +/- 6.9 vs. 9.5 +/- 2.8%; p = 0.11). In the subjects with LBP, psoas T2 asymmetry was significantly reduced immediately following OMT (25.3 +/- 6.9 to 6.1 +/- 1.8%, p = 0.05), and the change in LBP immediately following OMT was correlated with the change in psoas T2 asymmetry (r = 0.75, p = 0.02). CONCLUSION: Collectively, this pilot work demonstrates the feasibility of mfMRI for quantification and localization of muscle abnormalities in patients with acute low back pain. Additionally, this pilot work provides insight into the mechanistic actions of OMT during acute LBP, as it suggests that it may attenuate muscle activity asymmetries of some of the intrinsic low back muscles.
Clark, B. C., T. M. Manini, R. L. Hoffman, and D. W. Russ. 2009. “Restoration of Voluntary Muscle Strength After 3 Weeks of Cast Immobilization Is Suppressed in Women Compared With Men”. Arch Phys Med Rehabil 90: 178-80. https://doi.org/10.1016/j.apmr.2008.06.032.
OBJECTIVE: To investigate sex-related differences in the loss and recovery of voluntary muscle strength after immobilization. DESIGN: Longitudinal, repeated measures. SETTING: Research laboratory. PARTICIPANTS: Healthy men (n=5) and healthy women (n=5). INTERVENTION: Three weeks of forearm immobilization. MAIN OUTCOME MEASURES: Voluntary wrist flexion muscle strength was assessed at baseline and weekly during the immobilization protocol and 1 week after cast removal. Central activation was assessed before and after immobilization and after 1 week of recovery to determine what percentage of the muscle could be activated voluntarily. RESULTS: Men and women lost voluntary strength at a similar rate during immobilization. However, after 1 week of recovery voluntary strength had returned to within 1% of baseline in the men, but remained approximately 30% less than baseline in the women (P=0.03). Both sexes displayed reduced central activation after immobilization (P=0.02), but the decrease was similar in both sexes (P=0.82). CONCLUSIONS: These findings suggest sex-dependent adaptations to and recovery from limb immobilization, with voluntary strength recovering slower in women. As such, sex-specific rehabilitation protocols may be warranted, with women requiring additional or more intensive rehabilitation programs after periods of disuse. Future work is needed to determine the extent and mechanisms of these differences.
Clark, B. C. 2009. “In Vivo Alterations in Skeletal Muscle Form and Function After Disuse Atrophy”. Med Sci Sports Exerc 41: 1869-75. https://doi.org/10.1249/MSS.0b013e3181a645a6.
Prolonged reductions in muscle activity and mechanical loading (e.g., bed rest, cast immobilization) result in alterations in skeletal muscle form and function. The purpose of this review article was to synthesize recent findings from several studies on the dramatic effects of disuse on skeletal muscle morphology and muscle performance in humans. Specifically, the following are discussed: 1) how the antigravity muscles are most susceptible to atrophy and how the degree of atrophy varies between muscle groups; 2) how disuse alters muscle composition by increasing intermuscular adipose tissue; 3) the influence of different disuse models on regulating the loss of muscle mass and strength, with immobilization causing greater reductions than bed rest and limb suspension do; 4) the observation that disuse decreases strength to a greater extent than muscle mass and the role of adaptations in both neural and contractile properties that influences this excessive loss of strength; 5) the equivocal findings on the effect of disuse on muscle fatigue resistance; and 6) the reduction in motor control after prolonged disuse. Lastly, emerging data warranting further inquiry into the modulating role of biological sex on disuse-induced adaptations are also discussed.

2008

Damron, L. A., D. J. Dearth, R. L. Hoffman, and B. C. Clark. 2008. “Quantification of the Corticospinal Silent Period Evoked via Transcranial Magnetic Stimulation”. J Neurosci Methods 173: 121-8. https://doi.org/10.1016/j.jneumeth.2008.06.001.
A magnetic pulse to the cortex during a muscle contraction produces a motor evoked potential (MEP) followed by electrical quiescence before activity resumes that is indicative of corticospinal inhibition and commonly referred to as the corticospinal slient period (SP). The purpose of the present study was to determine the effect of stimulus intensity and quantification method on the between-visit variability of the SP in healthy individuals. On two occasions we recorded the SP from 9 humans at 3 stimulus intensities (10, 20 and 30% above active motor threshold [AMT]) and quantified the SP based on 8 common criteria. We evaluated the effect of stimulus intensity on reliability by using the limits of agreement, and this analysis revealed that the lower stimulus intensities (10 and 20% AMT) exhibited heteroscedasticity, which indicates the amount of random error increases as the silent period increases. The 30% AMT intensity was homoscedastic. We used both visual and mathematical approaches to quantify the SP, and observed that the between-visit coefficient of variation (CV) was less for the visual methods, and that the CV was reduced when the SP onset was earliest in the temporal occurrence of events (i.e. MEP onset to EMG return CV=12%). Inter-rater reliability for the visual analyses were high (r=0.91-0.99). These results suggest that SPs evoked with a stimulus intensity >or=30% AMT and quantified visually by defining the start of the SP at stimulus delivery or the start of the MEP be utilized to decrease the between visit variability.
Cowley, P. M., B. C. Clark, and L. L. Ploutz-Snyder. 2008. “Kinesthetic Motor Imagery and Spinal Excitability: The Effect of Contraction Intensity and Spatial Localization”. Clin Neurophysiol 119: 1849-56. https://doi.org/10.1016/j.clinph.2008.04.004.
OBJECTIVE: Data on whether motor imagery (MI) modulates spinal excitability are equivocal. The purpose of this study was to determine if imagined muscle contractions of the left plantar flexor (PF) alter spinal excitability, and if so, to determine whether this alteration is intensity dependent and/or localized to the target muscles. Our research questions required two experiments. METHODS: In experiment 1, 16 healthy volunteers performed imagined muscle contractions using a kinesthetic approach with their left PF at 25% and 100% of imagined effort (IE). The soleus H-reflex was evoked during three conditions, which were separated by about 15s: rest (preceding MI), during MI, and recovery (following the cessation of MI). In experiment 2, a subset of subjects from experiment 1 performed MI with their left PF at 100% of IE, while either the soleus or flexor carpi radialis (FCR) H-reflex was measured. RESULTS: In experiment 1, we observed a facilitation of soleus H-wave amplitude during MI compared to the rest and recovery conditions (p0.05). Furthermore, the soleus H-wave amplitude was greater during 100% than 25% of IE (p0.05). In experiment 2, soleus and FCR H-wave amplitude increased during imagined muscle contractions of the left PF (p0.05). These changes were independent of voluntary muscle activity. CONCLUSIONS: These findings suggest MI can increase spinal excitability by the intensity of imagined effort, but this effect is not fully localized to the task specific muscle. SIGNIFICANCE: These data provide evidence that MI can increase spinal excitability in healthy subjects, which suggests future studies are warranted to examine the clinical relevance of this effect. These studies are needed to help establish a therapeutic theory by which to advance motor function rehabilitation using MI.
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.