Publications

2025

Mahato, Niladri Kumar, Buket Sonbas Cobb, Seward B Rutkove, David Arnold, and Brian C Clark. (2025) 2025. “Multi-Frequency Electrical Impedance Myography As a Predictor of Muscle Function in Older Adults.”. Muscle & Nerve. https://doi.org/10.1002/mus.28449.
Publisher's Version

INTRODUCTION/AIMS: This study examined the potential of multi-frequency electrical impedance myography (EIM) to predict hand grip strength (HGS) variability among adults, including a large proportion of older adults, with and without sarcopenia. The objective was to develop predictive models using EIM data for assessing HGS and to explore its potential use in clinical evaluations of muscle function.

METHODS: Seventy-three participants aged 18-93 years were recruited at community events, with 69 completing EIM and HGS assessments. EIM data were collected from the forearm flexor and extensor muscle groups, and regression techniques, including Lasso regression, were applied to develop predictive models.

RESULTS: Approximately 60% of participants were over 65 years old, and 23% exhibited HGS values below sarcopenia thresholds. EIM measurements explained 48% of the variance in HGS. Adding demographic factors (sex, age, BMI) improved the explained variance to 64%, highlighting EIM's potential in muscle health assessments.

DISCUSSION: The findings suggest that multi-frequency EIM shows potential as a non-invasive tool for predicting HGS and assessing muscle function, particularly in aging populations. Further research is needed to fully establish EIM's utility in clinical settings for the early detection and management of sarcopenia.

Clark, Brian C. (2025) 2025. “Blue Plaque Review Series: Dr. Florence Buchanan: A Trailblazing Physiologist in an Era of Barriers and Breakthroughs.”. Experimental Physiology. https://doi.org/10.1113/EP092228.
Publisher's Version

What do Charles Darwin, T.H. Huxley, August Krogh and Charles Sherrington have in common? Florence Buchanan - a name history has unjustly dimmed but never erased. Her academic lineage is a direct thread through the titans of biology: E. Ray Lankester mentored her after being shaped by Huxley, Darwin's celebrated protégé. Buchanan's early career flourished under the mentorship of John Scott Burdon-Sanderson, but it was as an independent scientist that she collaborated with Nobel laureates Krogh and Sherrington, cementing her place among the greatest physiologists of her era. While accolades marked her career - a doctor of science, prestigious fellowships and groundbreaking publications - her path was anything but easy. As the first woman to attend meetings of The Physiological Society, she broke barriers but faced systemic exclusions, barred from The Society's dinners where scientific relationships were forged. Buchanan's meticulous experiments revealed muscles' intrinsic electrical rhythms and reshaped how physiology understands the neural control of the heart. Though her contributions were celebrated in her time, they were often overshadowed by her male colleagues. Who was this trailblazer whose scientific rigor and resilience quietly shaped modern physiology?

Kieser, Jacob, Matthew Langford, Emily Stover, Grant R Tomkinson, Brian C Clark, Peggy M Cawthon, and Ryan McGrath. (2025) 2025. “Absolute Agreement Between Subjective Hand Squeeze and Objective Handgrip Strength in Adults.”. Journal of Strength and Conditioning Research 39 (1): 16-23. https://doi.org/10.1519/JSC.0000000000004936.
Publisher's Version

Kieser, J, Langford, M, Stover, E, Tomkinson, GR, Clark, BC, Cawthon, PM, and McGrath, R. Absolute agreement between subjective hand squeeze and objective handgrip strength in adults. J Strength Cond Res 39(1): 16-23, 2025-Despite handgrip strength (HGS) being considered a convenient muscle strength assessment, HGS lacks routine measurement in sports medicine and healthcare settings because barriers such as time and lack of instrumentation may exist. Alternatives to circumvent these barriers should be sought. This study examined the absolute agreement of a subjective estimate of strength capacity on objectively measured HGS in adults aged 18-84 years. We also evaluated the test-retest reliability of an electronic handgrip dynamometer as a secondary purpose. There were 4 trained interviewers (i.e., assessors) who were assigned completely at random to subject laboratory visits occurring on 2 separate days. Trained interviewers carefully positioned their fingers into the hand of each subject before asking them to squeeze their fingers with maximal effort, and interviewers estimated each subject's HGS. An electronic handgrip dynamometer objectively measured HGS. Intraclass correlation coefficients (ICCs) were used for the analyses. The analytic sample included 100 subjects (age: 48.0 ± 20.2 years; 61% women). Poor agreement between mean objective HGS and averaged subjective hand squeeze was observed (ICC: 0.47; 95% confidence interval [CI]: 0.40-0.53). However, there was moderate agreement between dynamometer-derived maximal HGS and the most accurate HGS estimate (ICC: 0.75; CI: 0.65-0.86). An excellent test-retest reliability was found for mean (ICC: 0.97; CI: 0.95-0.98) and maximal HGS with the electronic dynamometer (ICC: 0.97; CI: 0.96-0.98). Trained interviewers performing subjective hand squeezes can approximate objective HGS with adequate accuracy, which could be useful when time and handgrip dynamometry access are lacking. Expanded interviewer training and testing may help with implementation.

2024

Seethapathi, Nidhi, Barrett C Clark, and Manoj Srinivasan. (2024) 2024. “Exploration-Based Learning of a Stabilizing Controller Predicts Locomotor Adaptation.”. Nature Communications 15 (1): 9498. https://doi.org/10.1038/s41467-024-53416-w.
Publisher's Version

Humans adapt their locomotion seamlessly in response to changes in the body or the environment. It is unclear how such adaptation improves performance measures like energy consumption or symmetry while avoiding falling. Here, we model locomotor adaptation as interactions between a stabilizing controller that reacts quickly to perturbations and a reinforcement learner that gradually improves the controller's performance through local exploration and memory. This model predicts time-varying adaptation in many settings: walking on a split-belt treadmill (i.e. with both feet at different speeds), with asymmetric leg weights, or using exoskeletons - capturing learning and generalization phenomena in ten prior experiments and two model-guided experiments conducted here. The performance measure of energy minimization with a minor cost for asymmetry captures a broad range of phenomena and can act alongside other mechanisms such as reducing sensory prediction error. Such a model-based understanding of adaptation can guide rehabilitation and wearable robot control.

2023

Spiering, B. A., B. C. Clark, B. J. Schoenfeld, S. A. Foulis, and S. M. Pasiakos. 2023. “Maximizing Strength: The Stimuli and Mediators of Strength Gains and Their Application to Training and Rehabilitation”. J Strength Cond Res 37: 919-29. https://doi.org/10.1519/JSC.0000000000004390.
Spiering, BA, Clark, BC, Schoenfeld, BJ, Foulis, SA, and Pasiakos, SM. Maximizing strength: the stimuli and mediators of strength gains and their application to training and rehabilitation. J Strength Cond Res 37(4): 919-929, 2023-Traditional heavy resistance exercise (RE) training increases maximal strength, a valuable adaptation in many situations. That stated, some populations seek new opportunities for pushing the upper limits of strength gains (e.g., athletes and military personnel). Alternatively, other populations strive to increase or maintain strength but cannot perform heavy RE (e.g., during at-home exercise, during deployment, or after injury or illness). Therefore, the purpose of this narrative review is to (a) identify the known stimuli that trigger gains in strength; (b) identify the known factors that mediate the long-term effectiveness of these stimuli; (c) discuss (and in some cases, speculate on) potential opportunities for maximizing strength gains beyond current limits; and (d) discuss practical applications for increasing or maintaining strength when traditional heavy RE cannot be performed. First, by conceptually deconstructing traditional heavy RE, we identify that strength gains are stimulated through a sequence of events, namely: giving maximal mental effort, leading to maximal neural activation of muscle to produce forceful contractions, involving lifting and lowering movements, training through a full range of motion, and (potentially) inducing muscular metabolic stress. Second, we identify factors that mediate the long-term effectiveness of these RE stimuli, namely: optimizing the dose of RE within a session, beginning each set of RE in a minimally fatigued state, optimizing recovery between training sessions, and (potentially) periodizing the training stimulus over time. Equipped with these insights, we identify potential opportunities for further maximizing strength gains. Finally, we identify opportunities for increasing or maintaining strength when traditional heavy RE cannot be performed.
McGrath, R., J. J. Lang, B. C. Clark, P. M. Cawthon, K. Black, J. Kieser, B. J. Fraser, and G. R. Tomkinson. 2023. “Prevalence and Trends of Handgrip Strength Asymmetry in the United States”. Adv Geriatr Med Res 5. https://doi.org/10.20900/agmr20230006.
BACKGROUND: Strength asymmetries are a type of muscle function impairment that is associated with several health conditions. However, the prevalence of these asymmetries among adults from the United States remains unknown. We sought to estimate the prevalence and trends of handgrip strength (HGS) asymmetry in American adults. METHODS: The unweighted analytic sample included 23,056 persons aged at least 50-years with information on HGS for both hands from the 2006-2016 waves of the Health and Retirement Study. A handgrip dynamometer measured HGS, with the highest recorded values for each hand used to calculate asymmetry. Persons were categorized into the following asymmetry severity categories: (1) >10%, (2) >20.0%, and (3) >30.0%. Survey weights were used to generate nationally-representative asymmetry estimates. RESULTS: Overall, there were no statistically significant trends in HGS asymmetry categories over time. The prevalence of HGS asymmetry in the 2014-2016 wave was 53.4% (CI: 52.2-54.4), 26.0% (CI: 25.0-26.9), and 11.7% (CI: 10.9-12.3) for asymmetry at >10%, >20%, and >30%, respectively. HGS asymmetry was generally higher in older Americans compared to middle-aged adults at each wave. In the 2014-2016 wave, >30% asymmetry prevalence was 13.7% (CI: 12.7-14.6) in females and 9.3% (CI: 8.4-10.2) in males. Some differences in asymmetry prevalence by race and ethnicity were observed. CONCLUSIONS: The prevalence of asymmetry was generally high, especially in women and older adults. Ongoing surveillance of strength asymmetry will help monitor trends in muscle dysfunction, guide screening for disablement, identify subpopulations at risk for asymmetry, and inform relevant interventions.
Criss, C. R., A. S. Lepley, J. A. Onate, B. C. Clark, J. E. Simon, C. R. France, and D. R. Grooms. 2023. “Brain Activity Associated With Quadriceps Strength Deficits After Anterior Cruciate Ligament Reconstruction”. Sci Rep 13: 8043. https://doi.org/10.1038/s41598-023-34260-2.
Prolonged treatment resistant quadriceps weakness after anterior cruciate ligament reconstruction (ACL-R) contributes to re-injury risk, poor patient outcomes, and earlier development of osteoarthritis. The origin of post-injury weakness is in part neurological in nature, but it is unknown whether regional brain activity is related to clinical metrics of quadriceps weakness. Thus, the purpose of this investigation was to better understand the neural contributions to quadriceps weakness after injury by evaluating the relationship between brain activity for a quadriceps-dominated knee task (repeated cycles of unilateral knee flexion/extension from 45 degrees to 0 degrees ), , and strength asymmetry in individuals returned to activity after ACL-R. Forty-four participants were recruited (22 with unilateral ACL reconstruction; 22 controls) and peak isokinetic knee extensor torque was assessed at 60 degrees /s to calculate quadriceps limb symmetry index (Q-LSI, ratio of involved/uninvolved limb). Correlations were used to determine the relationship of mean % signal change within key sensorimotor brain regions and Q-LSI. Brain activity was also evaluated group wise based on clinical recommendations for strength (Q-LSI 90%, n = 12; Q-LSI >/= 90%, n = 10; controls, all n = 22 Q-LSI >/= 90%). Lower Q-LSI was related to increased activity in the contralateral premotor cortex and lingual gyrus (p .05). Those who did not meet clinical recommendations for strength demonstrated greater lingual gyrus activity compared to those who met clinical recommendations Q-LSI >/= 90 and healthy controls (p 0.05). Asymmetrically weak ACL-R patients displayed greater cortical activity than patients with no underlying asymmetry and healthy controls.
Criss, C. R., A. S. Lepley, J. A. Onate, J. E. Simon, C. R. France, B. C. Clark, and D. R. Grooms. 2023. “Neural Correlates of Self-Reported Knee Function in Individuals After Anterior Cruciate Ligament Reconstruction”. Sports Health 15: 52-60. https://doi.org/10.1177/19417381221079339.
BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common knee injury among athletes and physically active adults. Despite surgical reconstruction and extensive rehabilitation, reinjuries are common and disability levels are high, even years after therapy and return to activity. Prolonged knee dysfunction may result in part from unresolved neuromuscular deficits of the surrounding joint musculature in response to injury. Indeed, "upstream" neurological adaptations occurring after injury may explain these persistent functional deficits. Despite evidence for injury consequences extending beyond the joint to the nervous system, the link between neurophysiological impairments and patient-reported measures of knee function remains unclear. HYPOTHESIS: Patterns of brain activation for knee control are related to measures of patient-reported knee function in individuals after ACL reconstruction (ACL-R). STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: In this multicenter, cross-sectional study, participants with unilateral ACL-R (n = 25; 10 men, 15 women) underwent task-based functional magnetic resonance imaging testing. Participants performed repeated cycles of open-chain knee flexion/extension. Neural activation patterns during the movement task were quantified using blood oxygen level-dependent (BOLD) signals. Regions of interest were generated using the Juelich Histological Brain Atlas. Pearson product-moment correlations were used to determine the relationship between mean BOLD signal within each brain region and self-reported knee function level, as measured by the International Knee Documentation Committee index. Partial correlations were also calculated after controlling for time from surgery and sex. RESULTS: Patient-reported knee function was positively and moderately correlated with the ipsilateral secondary somatosensory cortex (r = 0.57, P = 0.005) and the ipsilateral supplementary motor area (r = 0.51, P = 0.01). CONCLUSION: Increased ipsilateral secondary sensorimotor cortical activity is related to higher perceived knee function. CLINICAL RELEVANCE: Central nervous system mechanisms for knee control are related to subjective levels of knee function after ACL-R. Increased neural activity may reflect central neuroplastic strategies to preserve knee functionality after traumatic injury.
Clark, B. C. 2023. “Neural Mechanisms of Age-Related Loss of Muscle Performance and Physical Function”. J Gerontol A Biol Sci Med Sci 78: 8-13. https://doi.org/10.1093/gerona/glad029.
BACKGROUND: This article discusses the putative neural mechanisms of age-related muscle weakness within the broader context of the development of function-promoting therapies for sarcopenia and age-related mobility limitations. We discuss here the evolving definition of sarcopenia and its primary defining characteristic, weakness. METHODS: This review explores the premise that impairments in the nervous system's ability to generate maximal force or power contribute to sarcopenia. RESULTS: Impairments in neural activation are responsible for a substantial amount of age-related weakness. The neurophysiological mechanisms of weakness are multifactorial. The roles of supraspinal descending command mechanisms, spinal motor neuron firing responsivity, and neuromuscular junction transmission failure in sarcopenia are discussed. Research/clinical gaps and recommendations for future work are highlighted. CONCLUSION: Further research is needed to map putative neural mechanisms, determine the clinical relevance of age-related changes in neural activation to sarcopenia, and evaluate the effectiveness of various neurotherapeutic approaches to enhancing physical function.