Jason R. Franz - US grants

Our aging population is at an exceptionally high risk of debilitating falls, contributing significantly to reduced independence and quality of life. Despite conventional diagnostic and rehabilitative efforts, one-third of people over age 65 fall annually and 20-30% of these falls lead to moderate to severe injury. Remarkably, evidence even suggests that the rate of injurious falls among older adults is accelerating. Through an innovative sensorimotor paradigm using optical flow perturbations in a custom virtual environment, this proposal seeks to address the critical and immediate need for transformative new approaches for identifying and mitigating falls risk in our aging population. Our overarching goal is to investigate the efficacy of optical flow perturbations, particularly when applied during walking, to: (i) elucidate aging and falls history effects on standing and walking balance control, and (ii) subsequently condition successful balance control strategies through training. The first aim will tightly integrate virtual reality, visuomotor entrainment (i.e., the instinctive synchronization of motor responses to visual stimuli), and a series of clinical and self-reported benchmarks to investigate aging and falls history effects on the response to optical flow perturbations during standing and walking. We will test the hypothesis that optical flow perturbations during walking will distinguish age and falls history more effectively than those during standing and with effect sizes larger than those from conventional balance testing. The second aim will investigate sensory, motor, and cognitive-motor mechanisms governing susceptibility to optical flow perturbations. Using a strategically-selected combination of outcome measures and multivariate modeling, we will test the hypothesis that entrainment to optical flow perturbations will correlate most strongly with visual dependence and decreased somatosensory function, alluding to an age-associated process of multi-sensory reweighting that will emerge most prominently in walking. Finally, our third aim is designed to gain preliminary insight into the efficacy of prolonged optical flow perturbations to condition strategies used to successfully control walking balance in older adult fallers. In a randomized cross-over design, older adults with a history of falls will complete two treadmill training sessions ? one with (i.e., ?training? session) and one without (i.e., ?control? session) dynamic optical flow perturbations. We will test the hypothesis that older adults with a history of falls will adapt to prolonged exposure to perturbations, conditioning their step to step adjustments in walking balance control and improving their response to unexpected balance challenges following training. This research represents an interdisciplinary collaboration involving experienced investigators in biomedical engineering, physical therapy, and motor control. Successful completion of this R21 will provide the necessary mechanistic and preliminary efficacy information needed to design larger diagnostic and intervention studies to determine the value and applicability of perturbed optical flow to mitigate fall risk. With the advent of wearable and low cost virtual reality technology, this proposal is both timely and clinically feasible.

ABSTRACT Older adults walk slower and with higher metabolic energy cost than younger adults, changes that reduce independence and quality of life. These functional impairments stem from precipitous reductions in ankle push- off power output that cannot be improved by conventional strength training. Growing evidence reveals that muscle activation patterns tuned to underlying triceps surae (TS) muscle-tendon structural properties facilitate an effective burst of ankle power output during push-off. This study addresses two key questions: (1) Do age- related changes in series-elastic Achilles tendon (AT) structural properties (i.e., stiffness, kT) disrupt the tuned neuromechanical function of the TS with cascading metabolic penalties? and (2) Can donning elastic exoskeletons in parallel with biological TS muscle-tendons alter structural stiffness and improve the neuromechanics and energy cost of walking in older adults? Specific Aim 1 will quantify how aging effects activation-dependent tuning of triceps surae muscle-Achilles tendon interaction dynamics. Using controlled loads on a dynomometer and physiological loads during treadmill walking, we will couple advanced, dual-probe cine ultrasound imaging of TS muscle fascicles and localized AT tissue with novel electromyographic biofeedback to assess individual contributions of muscle versus tendon (kM and kT) to overall TS muscle-tendon stiffness (kMT) over a full landscape of muscle activation. Combined with metabolic measurements, we will test the hypotheses that (1A) older adults have a more complaint AT (i.e., lower kT) than young adults and thus, (1Bi) in isolated muscle contractions at prescribed TS muscle activations, older adults operate at shorter TS muscle fascicle lengths, and (1Bii) during walking at matched speeds, in an attempt to maintain overall kMT, older adults increase TS muscle stiffness (i.e., higher kM) by shifting to higher activations with shorter fascicle lengths than young adults -- with energetic implications at the (1) individual TS muscle (force per unit activation) and (b) whole- body (walking economy) levels. Specific Aim 2 will determine how elastic ankle exoskeletons alter the neuromechanics and energetics of walking in older adults ? from whole-body to individual muscles. Using a novel ankle exoskeleton emulator we will apply a range of exo-tendons (kEXO) in parallel with the TS muscle- tendon (kMT) while older adults walk at a fixed treadmill speed. We will test the hypotheses that (2A) older adults using elastic ankle exoskeletons will demonstrate reduced TS muscle activation and longer TS muscle fascicle operating lengths, and (2B) for older adults, the kEXO that most closely normalizes TS muscle-tendon stiffness (kMT) to that of their size-matched, young counterparts will yield the most youthful walking performance, evidenced by: (i) largest increase in ankle push-off power output and (ii) largest reduction in metabolic energy cost. Ultimately, this work will establish a framework for using ultrasound imaging to guide optimal prescription of assistive devices that can effectively modify the structure of the ankle triceps surae muscle-tendons to improve locomotor function in aging ? an outcome that will have significant positive impact on quality of life for millions.

Abstract Optimal mechanical loading is critical for joint tissue health, yet it remains unclear how to optimize loading following knee injury to prevent posttraumatic osteoarthritis (PTOA). The investigators' long-term goal is to develop individualized intervention strategies that target mechanical joint loading for the purpose of preventing PTOA. The objective of this R21 is to determine the acute effect of manipulating mechanical loading, using a real-time feedback paradigm to cue high-loading, low-loading and symmetrical loading conditions, on biomechanical, biochemical and structural measures related to PTOA pathogenesis in humans with anterior cruciate ligament reconstruction (ACLR). Recent evidence from the investigators' laboratory suggests that low- loading following injury may result in deleterious tissue metabolism and worse outcomes. Accordingly, the central hypothesis of this study is that the high-loading condition will result in greater tibiofemoral contact forces but also more knee excursion (less knee stiffness), resulting in a lesser immediate and delayed serum Cartilage Oligomeric Matrix Protein (COMP) response, as well as lesser cartilage deformation. The proposed study is needed because there is growing evidence, contrary to conventional theory, suggesting that patients with lesser mechanical loading following injury may be at higher risk for PTOA, and an intervention that cues higher-loading may be essential in mitigating that risk. Our study will demonstrate how manipulating mechanical load influences multiple critical outcomes needed to understand the mechanistic links between knee biomechanics, COMP response, and cartilage deformation. The central hypothesis will be tested with these two specific aims: 1) determine the acute effects of high-loading, low-loading, and symmetrical loading of the lower extremity on knee kinematics, knee kinetics and tibiofemoral joint contact forces during walking; 2) determine the effects of high-loading, low-loading and symmetrical loading during walking on serum COMP concentrations (immediately post and 3.5 hours post loading) and immediate sonography outcomes of femoral cartilage deformation. The proposed work is innovative as it: 1) incorporates a highly novel combination of outcome measures (biomechanical, joint tissue metabolism, and ultrasound of cartilage structure) that will lead to unprecedented mechanistic insight into the pathogenesis of PTOA; 2) strategically manipulates mechanical loading in multiple directions to determine how a known change in mechanical load will acutely influence outcomes, which is a stark departure from previous cross-sectional studies; and 3) utilizes a novel real-time feedback paradigm to cue changes in mechanical joint loading, which can easily be further developed into a future intervention. This R21 is significant, as the results will be pivotal in understanding how low-loading, high-loading and symmetrical loading influence changes in biomechanical, biochemical and cartilage deformation outcomes, which will lead to unprecedented mechanistic insight into PTOA pathogenesis and provide critical information regarding how best to direct loading following injury to prevent PTOA onset.  

PROJECT SUMMARY Despite conventional diagnostic and rehabilitative efforts, and a rich understanding of standing balance control, our rapidly aging population remains at an exceptionally high risk of debilitating falls. A major contributor to this continued risk is that most falls occur during everyday walking tasks which are much less well understood and require more complex neuromuscular coordination. Our long-term goal is to introduce a novel neuromuscular mechanism for age-associated walking balance impairment as a strategic target for diagnostic testing, earlier prevention, and rehabilitation to prevent falls in older adults. We posit that all individuals rely on a principal number of peripheral neuromuscular commands ? a ?peripheral motor repertoire? ? to accomplish everyday walking tasks during which falls may occur (e.g., walking, turning, gait initiation, precision stepping). Supported by promising pilot data, the objective of this R21 is to rigorously test the overarching hypothesis that a reduced peripheral motor repertoire used for everyday walking tasks represents a neuromuscular constraint on older adults? ability to successfully respond to walking balance perturbations and thereby prevent falls in the community. This cross-sectional study has three aims. Specific Aim 1 will test the hypothesis that the peripheral motor repertoire (i.e., number of motor modules or muscle synergies) used to accomplish everyday walking tasks is reduced by falls history more than by age alone and negatively correlates with the number falls in the prior year. Specific Aim 2 will quantify the association between the peripheral motor repertoire, functional balance integrity, and fear of future falls. Here, we will test the hypothesis that the size of the peripheral motor repertoire used during everyday walking tasks associates more with functional balance integrity than fear of future falls. We will interpret this finding as evidence that a reduced peripheral motor repertoire represents a neuromuscular constraint that precipitates poor balance control versus an emergent strategy associated with a fear of recurrent falls. Specific Aim 3 will test the hypothesis that a reduced peripheral motor repertoire associates with larger susceptibility to a diverse combination of sensory and mechanical balance perturbation paradigms applied during walking. We will interpret this finding as a critical mechanistic link between the peripheral motor repertoire used during everyday walking tasks and ability to accommodate balance challenges relevant to falls in the community. The proposed study is innovative, and the first to combine: (1) state-of-the-art electromyographic analyses across everyday walking tasks during which falls may occur in young adults and in older adults with and without a history of falls, (2) functional and neuropsychological measures of walking balance integrity, balance self- efficacy, and fear of future falls, and (3) a combination of sensory and mechanical balance perturbation paradigms applied during walking. This project will provide pivotal insight into a very specific and innovative feature of neuromuscular control as a mechanism for age-related balance impairment while paving the way for planned prospective studies toward more effective targets for diagnostics and rehabilitation to prevent falls.