Publications

2010

Clark, B. C., J. L. Taylor, R. L. Hoffman, D. J. Dearth, and J. S. Thomas. 2010. “Cast immobilization increases long-interval intracortical inhibition”. Muscle Nerve 42: 363-72. https://doi.org/10.1002/mus.21694.
Immobilization reduces muscle performance, and despite these performance losses being associated with neural impairments little is known regarding adaptations in cortical properties. We utilized transcranial magnetic stimulation to assess changes in flexor carpi radialis (FCR) intracortical facilitation (ICF), and short- and long-interval intracortical inhibition (SICI and LICI) in healthy humans undergoing 3 weeks of immobilization. Measurements were obtained at rest and during contraction (15% intensity). Central activation and the Hoffman reflex (H-reflex) were also assessed. Strength decreased 43.2% +/- 6.1% following immobilization, and central activation also decreased (97.5% +/- 2.4% to 73.2% +/- 8.3%). No changes in ICF, SICI, or LICI were observed at rest; however, LICI was increased during contraction (67.5% +/- 6.9% to 53.1% +/- 6.7% of unconditioned response). The increase in LICI correlated with the loss of strength (r = -0.63). The H-reflex increased following immobilization. These findings suggest that immobilization increases intracortical inhibition during contraction, and this increase is primarily mediated by GABA(B) receptors.
Clark, B. C., and T. M. Manini. 2010. “Functional consequences of sarcopenia and dynapenia in the elderly”. Curr Opin Clin Nutr Metab Care 13: 271-6. https://doi.org/10.1097/MCO.0b013e328337819e.
PURPOSE OF REVIEW: The economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article, we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed. RECENT FINDINGS: Recent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia. SUMMARY: Although muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood and further research is needed to better elucidate these mechanisms between muscle groups and across populations.

2009

Manini, T. M., and B. C. Clark. 2009. “Blood flow restricted exercise and skeletal muscle health”. Exerc Sport Sci Rev 37: 78-85. https://doi.org/10.1097/JES.0b013e31819c2e5c.
For nearly half a century, high mechanical loading and mechanotransduction pathways have guided exercise recommendations for inducing muscle hypertrophy. However, emerging research on low-intensity exercise with blood flow restriction challenges this paradigm. This article will describe the BFR exercise model and discuss its efficacy, potential mechanisms, and clinical viability.
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.