Gregory S. Sawicki - US grants

[unreadable] DESCRIPTION (provided by applicant): Project Summary: Elastic energy storage and return in tendons can save significant metabolic energy, but likely requires muscle force patterns with precise timing and magnitude. Neuromuscular and neurological impairments (e.g. stroke, spinal cord injury, cerebral palsy) and powered lower-limb robotic assistive devices can lead to altered patterns of muscle force output during locomotion. The broad goal of this research is to examine how tendon elasticity effects the mechanics of the contractile element of the musle-tendon unit under conditions of reduced muscle force output. The project will use an isolated muscle-tendon preparation and modeling, to test several hypotheses about the role of tendons in modulating muscle work during cyclic contraction. The specific aims are to (1) show that contractile element work does not decrease in proportion to muscle force during stretch-shorten contractions and (2) determine the effect of relative tendon compliance (i.e. the ratio of tendon length to muscle-tendon length) on the force-work relationship of the contractile element of muscle-tendon. The in vitro experiments will use a novel combination of sonomicrometry and muscle ergometry to separate the mechanical behavior of the muscle from the tendon during controlled stretch-shortening of bullfrog (Rana catesbeiana L.) plantaris longus muscle-Achilles tendon. To complement the in vitro experiments I will build an equivalent computer simulation of the muscle- tendon unit. Non-linear equations will characterize the force-length, force-velocity and force-activation properties of the contractile element and a linear spring will represent the series-elastic element. The rationale behind combining empirical and theoretical approaches is that (1) the muscle-tendon model can make predictions to be tested with carefully designed in vitro experiments and (2) the in vitro experiments on muscle-tendon can help test the validity of model simplifications. The proposed research will develop skills in both muscle physiology and non-linear computational modeling that will be invaluable to my future research program to develop bio-inspired lower limb assistive devices. Relevance: A fundamental understanding of integrated muscle-tendon function has important implications for solving problems relevant to human health. The proposed project will attract interdisciplinary interest from clinicians, physiologists, biomechanists, and engineers. The results will (1) aid in developing strategies for the rehabilitation of neurological and musculoskeletal disorders that limit muscle force production (2) contribute to improved design of prostheses and orthoses intended to assist the lower-limb during gait. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Although cystic fibrosis (CF) is the most common life-limiting genetic disease in the Caucasian population, survival has increased such that many more children and adolescents with CF are living well into adulthood. This increased survival has led to new opportunities and challenges in the care of adolescents and young adults with CF. One major challenge is how best to prepare adolescents and families for the transition from pediatric to adult-centered health care during a time in which CF disease may worsen and challenges of chronic disease self-management increase. Dr. Sawicki is an Assistant Professor of Pediatrics at Harvard Medical School and a pediatric pulmonologist at the CF Center at Children's Hospital Boston. His principal areas of interest are health outcomes and quality improvement, particularly focused on the vulnerable period of health care transition for adolescents and young adults with CF. Dr. Sawicki's immediate career goal is to develop expertise in clinical outcomes research of children with complex chronic medical conditions. He completed a fellowship in pediatric health services research, but requires further training through formal coursework in advanced research methods and analytic techniques. He will work with a mentorship team led by national experts in the fields of CF health outcomes research, qualitative research, and health care transition. His long-term career goal is to become an independent researcher with expertise in health outcomes and healthcare delivery systems for adolescents with CF, with the long-term objective of investigating how interventions during adolescence can lead to sustained improvements in self-management and health outcomes when these patients reach adulthood. The work and research in his career development proposal complement the mission for NHLBI. Dr. Sawicki will perform a study of health care transition among adolescents and young adults with CF. The aims of this proposal are: 1) To understand the barriers and facilitators of transition to adult care as perceived by adolescents with CF and their parents. 2) To examine longitudinal changes in transition readiness among a cohort of adolescents with CF, and 3) To examine the impact of illness perception, treatment beliefs, social support, disease severity, and health-related quality of life on the development and progression of health care transition readiness in a cohort of adolescents with CF. He will use both qualitative and longitudinal survey methodology in this project. This study will substantially contribute to the understanding of barriers and facilitators for health care transition among adolescents and young adults with CF. The results of this research may have significant implications for the delivery of healthcare in CF. In addition, this work may serve as a model for the study of health care transition for other populations of young adults with chronic medical conditions of childhood onset.

DESCRIPTION (provided by applicant): The objective of this project is to compare different techniques for assisting individuals with stroke-related mobility impairments using robotic ankle orthoses. Several promising assistance techniques have been developed for robotic prostheses and rehabilitation platforms. Many of these, however, have not yet been applied to powered orthoses or exoskeletons, and few have been applied at the ankle joint, despite its importance in locomotion. The efficacy of these techniques has not been tested consistently, and techniques have not been optimized for individuals with stroke nor directly compared against each other. The proposed study addresses these needs by directly comparing physiological responses to different assistance techniques provided by a versatile robotic platform. A standardized set of quantitative performance metrics are proposed, including measures of effort, preferred speed, and stability. An ankle exoskeleton emulator, previously developed by the investigators, is proposed for use due to its unique ability to express a wide range of robotic functions in a single platform. Each promising technique will first be programmed and verified in pilot tests with the emulator. Multi-dimensional parameter studies will then be performed for each assistance technique, first on subjects without neurological impairment and then on subjects with hemiparesis following stroke. Results will be used to identify optimal parameters for each approach. Finally, an across-technique comparison will be performed using optimal parameters. These tests are expected to provide a scientific foundation for the design and prescription of robotic ankle-foot orthoses that manage symptoms for millions of individuals with stroke. Results will inform improved orthosis designs and test feasibility of designs that are both effective and low-cost. Together, these results are expected to provide the evidence base to make post-stroke care more effective, less expensive, and manageable by fewer clinical practitioners, addressing the needs of our aging population and potentially leading to reduced disparities in treatment.

DESCRIPTION (provided by applicant): Stroke is a leading cause of chronic disability in the United States, with nearly 610,000 new cases annually. In chronic stroke patients, slow, exhausting walking is a primary deleterious outcome that limits activities of daily living. Furthermore, impaired walking can lead to secondary impairments such as muscle weakness and poor balance, both risk factors for falls. Therefore, interventions designed to improve walking function post-stroke could have significant positive impact on the quality of life of millions. In healthy walking, the ankle extensor muscles play a major role in key walking sub-tasks including (1) propulsion (2) body-weight support and (3) swing initiation. Chronic stroke patients typically have problems with each of these sub-tasks, likely due to weak and uncoordinated ankle mechanical function in their paretic limb. Impaired unilateral ankle function results in highly asymmetric gait that limits top walking speed and elevates metabolic energy expenditure. The primary objective of the proposed research is to use a wearable robotic device to assist the paretic limb in patients with post-stroke hemiplegia and improve both gait symmetry and economy. We will recruit 20 patients with chronic stroke and construct lightweight robotic ankle exoskeletons for their paretic limb. Then we will test whether robotic assistance focused on ankle joint extension can improve paretic limb function - driving it towards that of size/age paired healthy controls. We hypothesize that targeted, unilateral ankle joint mechanical assistance will restore gait symmetry across multiple scales of musculoskeletal organization - from limbs to lower-limb joints- and reduce the metabolic cost of walking in people post-stroke. If robotic ankle exoskeletons can restore normal walking mechanics and reduce metabolic cost, then people with severe impairments post-stroke could benefit from a portable version as a permanent aid during community ambulation.

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.

PROJECT SUMMARY Our long-term goal is to identify neural mechanisms and the functional roles of sensorimotor signals in health and disease as needed to guide mechanistically targeted diagnoses, assessments, and treatments for neurological movement disorders. Here we address the scientific barriers to understanding and treating a broad class of movement disorder symptoms recently defined as joint hyper-resistance, which encompass spasticity in stroke, spinal cord injury, or cerebral palsy; parkinsonian rigidity, and hypertonia. The objective of this collaborative, interdisciplinary proposal is to identify neural mechanisms of hyper-resistance and dissociate their relative roles in abnormal movement. We will focus on the neural mechanisms underlying two clinically- defined neural contributions to hyper-resistance: non-velocity dependent involuntary background activation and velocity-dependent stretch hyper-reflexia. We hypothesize that increased spinal excitability in many neurological disorders causes involuntary background activation and velocity-dependent stretch hyper-reflexia via three dissociable neural mechanisms: 1) alpha-drive to extrafusal muscle fibers increasing background muscle tension, 2) gamma-drive to specialized intrafusal muscle fibers in muscle spindles sensory organs, increasing their sensitivity to muscle stretch, and 3) sensorimotor gain of the spinal transformation of monosynaptic sensory input into motor output. Our proposed tests of this hypothesis will advance understanding of the important, yet still unresolved relative contributions made by these neural mechanisms to hyper-resistance. Based on our neuromechanical and multiscale modeling advances in the prior funding period, in Aim 1 we will develop a multiscale in silico neuromuscular circuit model to predict how independent changes in alpha- drive, gamma-drive, and sensorimotor gain differentially affect clinically-relevant movements such as the tendon tap and pendulum test. In Aim 2, we will characterize the relative increases in alpha-drive, gamma-drive, and sensorimotor gain across clinically-relevant spinal excitability levels in a living biological neuromuscular circuit in vivo using a decerebrate rat preparation. In Aim 3 we will identify clinically-relevant movement abnormalities across spinal excitability levels in a novel biohybrid robotic system coupling the living neuromuscular circuit (in vivo) to a virtual biomechanical limb (in silico). A robotic controller will enforce the physics of dynamically changing inertial and gravitational forces, allowing movement to emerge from the causal interaction between the in vivo neuromuscular circuit and the virtual limb. Through the close coordination of these Aims, we will establish a computational and experimental framework to address clinical barriers (1) to determine how changes in neural mechanisms and the inertial properties of the limb could correct movement abnormalities, (2) to provide insight into how these mechanisms could be identified through different clinical assessment scenarios, and (3) to compare the relative effects of different treatment targets. The proposed work will likely impact both clinically-relevant human sensorimotor research and basic sensorimotor neuroscience.