Publications

2016

Mahato, N. K., S. Montuelle, J. Cotton, S. Williams, J. Thomas, and B. Clark. 2016. “Development of a Morphology-Based Modeling Technique for Tracking Solid-Body Displacements: Examining the Reliability of a Potential MRI-only Approach for Joint Kinematics Assessment”. BMC Med Imaging 16: 38. https://doi.org/10.1186/s12880-016-0140-1.
BACKGROUND: Single or biplanar video radiography and Roentgen stereophotogrammetry (RSA) techniques used for the assessment of in-vivo joint kinematics involves application of ionizing radiation, which is a limitation for clinical research involving human subjects. To overcome this limitation, our long-term goal is to develop a magnetic resonance imaging (MRI)-only, three dimensional (3-D) modeling technique that permits dynamic imaging of joint motion in humans. Here, we present our initial findings, as well as reliability data, for an MRI-only protocol and modeling technique. METHODS: We developed a morphology-based motion-analysis technique that uses MRI of custom-built solid-body objects to animate and quantify experimental displacements between them. The technique involved four major steps. First, the imaging volume was calibrated using a custom-built grid. Second, 3-D models were segmented from axial scans of two custom-built solid-body cubes. Third, these cubes were positioned at pre-determined relative displacements (translation and rotation) in the magnetic resonance coil and scanned with a T1 and a fast contrast-enhanced pulse sequences. The digital imaging and communications in medicine (DICOM) images were then processed for animation. The fourth step involved importing these processed images into an animation software, where they were displayed as background scenes. In the same step, 3-D models of the cubes were imported into the animation software, where the user manipulated the models to match their outlines in the scene (rotoscoping) and registered the models into an anatomical joint system. Measurements of displacements obtained from two different rotoscoping sessions were tested for reliability using coefficient of variations (CV), intraclass correlation coefficients (ICC), Bland-Altman plots, and Limits of Agreement analyses. RESULTS: Between-session reliability was high for both the T1 and the contrast-enhanced sequences. Specifically, the average CVs for translation were 4.31 % and 5.26 % for the two pulse sequences, respectively, while the ICCs were 0.99 for both. For rotation measures, the CVs were 3.19 % and 2.44 % for the two pulse sequences with the ICCs being 0.98 and 0.97, respectively. A novel biplanar imaging approach also yielded high reliability with mean CVs of 2.66 % and 3.39 % for translation in the x- and z-planes, respectively, and ICCs of 0.97 in both planes. CONCLUSIONS: This work provides basic proof-of-concept for a reliable marker-less non-ionizing-radiation-based quasi-dynamic motion quantification technique that can potentially be developed into a tool for real-time joint kinematics analysis.
Law, T. D., L. A. Clark, and B. C. Clark. 2016. “Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia”. Annu Rev Gerontol Geriatr 36: 205-28. https://doi.org/10.1891/0198-8794.36.205.
For well over twenty centuries the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern of mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades scientists have recognized the profound role that progressive resistance exercise training can have on increasing muscle strength, muscle size and functional capacity in older adults. In this review article we discuss how resistance exercise training can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors- namely exercise intensity, volume and progression- that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the 'best practices', and subsequently present easy-to-read guidelines for a well-rounded resistance exercise training program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health care provider across a variety of disciplines, including those in the long term care industry, such as wellness instructors or activity directors.
Amano, S., A. F. Ludin, R. Clift, M. Nakazawa, T. D. Law, L. J. Rush, T. M. Manini, J. S. Thomas, D. W. Russ, and B. C. Clark. 2016. “Effectiveness of Blood Flow Restricted Exercise Compared With Standard Exercise in Patients With Recurrent Low Back Pain: Study Protocol for a Randomized Controlled Trial”. Trials 17: 81. https://doi.org/10.1186/s13063-016-1214-7.
BACKGROUND: Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the "cross-transfer" of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes). METHODS AND STUDY DESIGN: This is a single-blinded, single-site, randomized controlled trial. A minimum of 32 (and up to 40) subjects aged 18 to 50 years with recurrent low back pain and poor trunk extensor muscle endurance will be recruited, enrolled and randomized. After completion of baseline assessments, participants will be randomized in a 1:1 ratio to receive a 10-week resistance exercise training program with blood flow restriction (BFR exercise group) or without blood flow restriction (control exercise group). Repeat assessments will be taken immediately post intervention and at 12 weeks after the completion of the exercise program. Furthermore, once every 4 weeks during a 36-week follow-up period, participants will be asked to rate their perceived disability and back pain over the past 14 days. DISCUSSION: This study will examine the potential for blood flow restricted exercise applied to appendicular muscles to result in a "cross-transfer" of therapeutic effect to the lumbar musculature in individuals with low back pain. The results of this study will provide important insights into the effectiveness of this novel exercise modality, which could potentially provide the foundation for a cost-effective and easy-to-implement rehabilitation strategy to induce muscle adaptation in the absence of high mechanical and compressive loading on the spine. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (registration number: NCT02308189, date of registration: 2 December 2014).

2015

Oki, K., T. D. Law, A. B. Loucks, and B. C. Clark. 2015. “The Effects of Testosterone and Insulin-Like Growth Factor 1 on Motor System Form and Function”. Exp Gerontol 64: 81-6. https://doi.org/10.1016/j.exger.2015.02.005.
In this perspective article, we review the effects of selected anabolic hormones on the motoric system and speculate on the role these hormones may have on influencing muscle and physical function via their impact on the nervous system. Both muscle strength and anabolic hormone levels decline around middle age into old age over a similar time period, and several animal and human studies indicate that exogenously increasing anabolic hormones (e.g., testosterone and insulin-like growth factor-1 (IGF-1)) in aged subjects is positively associated with improved muscle strength. While most studies in humans have focused on the effects of anabolic hormones on muscle growth, few have considered the impact these hormones have on the motoric system. However, data from animals demonstrate that administering either testosterone or IGF-1 to cells of the central and peripheral motor system can increase cell excitability, attenuate atrophic changes, and improve regenerative capacity of motor neurons. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines.
Clark, B. C., J. L. Taylor, S. L. Hong, T. D. Law, and D. W. Russ. 2015. “Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation”. J Gerontol A Biol Sci Med Sci 70: 1112-9. https://doi.org/10.1093/gerona/glv030.
BACKGROUND: Weakness predisposes seniors to a fourfold increase in functional limitations. The potential for age-related degradation in nervous system function to contribute to weakness and physical disability has garnered much interest of late. In this study, we tested the hypothesis that weaker seniors have impairments in voluntary (neural) activation and increased indices of GABAergic inhibition of the motor cortex, assessed using transcranial magnetic stimulation. METHODS: Young adults (N = 46; 21.2+/-0.5 years) and seniors (N = 42; 70.7+/-0.9 years) had their wrist flexion strength quantified along with voluntary activation capacity (by comparing voluntary and electrically evoked forces). Single-pulse transcranial magnetic stimulation was used to measure motor-evoked potential amplitude and silent period duration during isometric contractions at 15% and 30% of maximum strength. Paired-pulse transcranial magnetic stimulation was used to measure intracortical facilitation and short-interval and long-interval intracortical inhibition. The primary analysis compared seniors to young adults. The secondary analysis compared stronger seniors (top two tertiles) to weaker seniors (bottom tertile) based on strength relative to body weight. RESULTS: The most novel findings were that weaker seniors exhibited: (i) a 20% deficit in voluntary activation; (ii)  20% smaller motor-evoked potentials during the 30% contraction task; and (iii) nearly twofold higher levels of long-interval intracortical inhibition under resting conditions. CONCLUSIONS: These findings indicate that weaker seniors exhibit significant impairments in voluntary activation, and that this impairment may be mechanistically associated with increased GABAergic inhibition of the motor cortex.

2014

Williams, P. S., R. L. Hoffman, and B. C. Clark. 2014. “Cortical and Spinal Mechanisms of Task Failure of Sustained Submaximal Fatiguing Contractions”. PLoS One 9: e93284. https://doi.org/10.1371/journal.pone.0093284.
In this and the subsequent companion paper, results are presented that collectively seek to delineate the contribution that supraspinal circuits have in determining the time to task failure (TTF) of sustained submaximal contractions. The purpose of this study was to compare adjustments in supraspinal and spinal excitability taken concurrently throughout the performance of two different fatigue tasks with identical mechanical demands but different TTF (i.e., force-matching and position-matching tasks). On separate visits, ten healthy volunteers performed the force-matching or position-matching task at 15% of maximum strength with the elbow flexors to task failure. Single-pulse transcranial magnetic stimulation (TMS), paired-pulse TMS, paired cortico-cervicomedullary stimulation, and brachial plexus electrical stimulation were delivered in a 6-stimuli sequence at baseline and every 2-3 minutes throughout fatigue-task performance. Contrary to expectations, the force-matching task TTF was 42% shorter (17.5 +/- 7.9 min) than the position-matching task (26.9 +/- 15.11 min; p0.01); however, both tasks caused the same amount of muscle fatigue (p = 0.59). There were no task-specific differences for the total amount or rate of change in the neurophysiologic outcome variables over time (p>0.05). Therefore, failure occurred after a similar mean decline in motorneuron excitability developed (p0.02, ES = 0.35-0.52) coupled with a similar mean increase in measures of corticospinal excitability (p0.03, ES = 0.30-0.41). Additionally, the amount of intracortical inhibition decreased (p0.03, ES = 0.32) and the amount of intracortical facilitation (p>0.10) and an index of upstream excitation of the motor cortex remained constant (p>0.40). Together, these results suggest that as fatigue develops prior to task failure, the increase in corticospinal excitability observed in relationship to the decrease in spinal excitability results from a combination of decreasing intracortical inhibition with constant levels of intracortical facilitation and upstream excitability that together eventually fail to provide the input to the motor cortex necessary for descending drive to overcome the spinal cord resistance, thereby contributing to task failure.
Kaya, R. D., R. L. Hoffman, and B. C. Clark. 2014. “Reliability of a Modified Motor Unit Number Index (MUNIX) Technique”. J Electromyogr Kinesiol 24: 18-24. https://doi.org/10.1016/j.jelekin.2013.10.005.
INTRODUCTION: The purpose of this study was to examine the relative and absolute between-day reliability of the motor unit number index (MUNIX). METHODS: Young, healthy adults (n=19) attended two testing sessions separated by 4-weeks where their maximal pinch-grip strength, MUNIX, and motor unit size index (MUSIX) were assessed in the abductor pollicis brevis muscle. Reliability was assessed by intraclass correlation coefficients (ICC), coefficient of variation (CV) and limits of agreement (LOA). RESULTS: No mean differences were observed for MUNIX or MUSIX. The CV for the MUNIX and MUSIX measures were between 13.5% and 17.5%. The ICC for both measures were moderate to moderately-high (0.73-0.76), The LOA for both indicated a homoscedastic relationship. DISCUSSION: Our findings indicate moderate to moderately-high reliability for both MUNIX and MUSIX. Future work is needed to ensure both measures are reliable in other muscles and cohorts, and further investigations are required to examine the validity of MUNIX.