Publications

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.

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.

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.

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.

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.

Changes in old age that contribute to the complex issue of an increased metabolic cost of walking (mass-specific energy cost per unit distance traveled) in older adults appear to center at least in part on changes in gait biomechanics. However, age-related changes in energy metabolism, neuromuscular function and connective tissue properties also likely contribute to this problem, of which the consequences are poor mobility and increased risk of inactivity-related disease and disability. The U.S. National Institute on Aging convened a workshop in September 2021 with an interdisciplinary group of scientists to address the gaps in research related to the mechanisms and consequences of changes in mobility in old age. The goal of the workshop was to identify promising ways to move the field forward toward improving gait performance, decreasing energy cost, and enhancing mobility for older adults. This report summarizes the workshop and brings multidisciplinary insight into the known and potential causes and consequences of age-related changes in gait biomechanics. We highlight how gait mechanics and energy cost change with aging, the potential neuromuscular mechanisms and role of connective tissue in these changes, and cutting-edge interventions and technologies that may be used to measure and improve gait and mobility in older adults. Key gaps in the literature that warrant targeted research in the future are identified and discussed.

Sarcopenia, or age-related decline in muscle form and function, exerts high personal, societal, and economic burdens when untreated. Integrity and function of the neuromuscular junction (NMJ), as the nexus between the nervous and muscular systems, is critical for input and dependable neural control of muscle force generation. As such, the NMJ has long been a site of keen interest in the context of skeletal muscle function deficits during aging and in the context of sarcopenia. Historically, changes of NMJ morphology during aging have been investigated extensively but primarily in aged rodent models. Aged rodents have consistently shown features of NMJ endplate fragmentation and denervation. Yet, the presence of NMJ changes in older humans remains controversial, and conflicting findings have been reported. This review article describes the physiological processes involved in NMJ transmission, discusses the evidence that supports NMJ transmission failure as a possible contributor to sarcopenia, and speculates on the potential of targeting these defects for therapeutic development. The technical approaches that are available for assessment of NMJ transmission, whether each approach has been applied in the context of aging and sarcopenia, and the associated findings are summarized. Like morphological studies, age-related NMJ transmission deficits have primarily been studied in rodents. In preclinical studies, isolated synaptic electrophysiology recordings of endplate currents or potentials have been mostly used, and paradoxically, have shown enhancement, rather than failure, with aging. Yet, in vivo assessment of single muscle fiber action potential generation using single fiber electromyography and nerve-stimulated muscle force measurements show evidence of NMJ failure in aged mice and rats. Together these findings suggest that endplate response enhancement may be a compensatory response to post-synaptic mechanisms of NMJ transmission failure in aged rodents. Possible, but underexplored, mechanisms of this failure are discussed including the simplification of post-synaptic folding and altered voltage-gated sodium channel clustering or function. In humans, there is limited clinical data that has selectively investigated single synaptic function in the context of aging. If sarcopenic older adults turn out to exhibit notable impairments in NMJ transmission (this has yet to be examined but based on available evidence appears to be plausible) then these NMJ transmission defects present a well-defined biological mechanism and offer a well-defined pathway for clinical implementation. Investigation of small molecules that are currently available clinically or being testing clinically in other disorders may provide a rapid route for development of interventions for older adults impacted by sarcopenia.