Andrew A. Biewener - US grants

DESCRIPTION: (Adapted from investigator's abstract) The investigator's objective is to develop and use non-invasive approaches to evaluate: (1) the effect of physical exercise on the growing and mature skeleton; and (2) to relate these changes to correlated changes in the skeletal muscles and their tendons. They will examine the extent to which phenotypic plasticity of the vertebrate musculoskeletal system in an integrated response to exercise. These animal experiments will help increase the understanding of the design principles of the musculoskeletal system common to all animals, including humans, and will have potential application in rehabilitation and training of children and adults associated with physical activity. The model the investigators will use involves quantification of the bone's loading history by recording in vivo strain at functionally equivalent sites on the bone at specific time during the exercise period. Correspondingly, the loading history of the muscles and their tendons are determined using force-platform/kinematic analyses and direct in vivo tendon force recordings. Exercise is varied by running the animals on a treadmill at different speeds and duration, and by varying the loads that the animals carry on their backs. Known parameters of the loading history for the bone, muscles and tendons can then be related to quantified changes in their morphology, focusing on bone formation and resorption rates at sites where the tissues's strain history is known. Specifically, the following three hypotheses will be tested: (1) that bone models to maintain a uniform distribution of strain at functionally equivalent sites; (2) that disruption of the normal distribution of strain, rather than elevated strain per se, is most critical for eliciting adaptive bone modeling; and (3) that the mass and form of bone, muscle and tendon in an animals's limb is matched to maintain a similar safety factor to failure, providing integrated design to protect against injury or failure. To test these hypotheses, the investigators will quantify bone, muscle and tendon loading during treadmill exercise in growing chicks and hamsters. Matched experiments will be carried out on mature animals to compare the adaptive plasticity of mature versus growing bone, muscle and tendon. They will also, evaluate more precisely the extent to which disruption of normal strain gradients in the bone's cortex affects adaptive modeling responses of the bone.

This project seeks to understand how muscles function to power the flight of birds. Changes in muscle power requirements are expected over a range of speeds based on aerodynamic theory. By studying how muscles are activated to develop force and shorten under the dynamic conditions of flight, the predictions of flight performance based on aerodynamic models can be tested. These measurements will be obtained from ring-neck doves (Streptopelia risoria), cockatiels (Nymphicus hallandicus) and crows (Corvusbrachyrynchos) that have been trained to fly over a range of steady speeds (1 to 20 meters/second) in a low turbulence wind tunnel. The results obtained from these experiments will be used to evaluate whether the requirements for muscle performance are greatest during slow- and very fast-speed flight, compared with the lower costs predicted by aerodynamic theory at intermediate flight speeds. Comparisons among the different species will also allow the effects of differences in wing shape and body weight to be evaluated in relation to muscle function and flight performance. In addition to studies of the function of bird flight muscles, the project will also involve obtaining detailed recordings of the three-dimensional movements and shape changes of the wings (kinematics) during the wing beat cycle. These recordings will be obtained using three high-speed (250 frames per second) digital video cameras . Movements of the wings and changes in their shape and orientation will be examined over a range of flight speeds in the wind tunnel to evaluate whether the birds use distinct aerodynamic gaits to fly at slow versus fast speeds, similar to the change in gait that a human uses when increasing speed from a walk to a run. By correlating movements of the wing with the recordings of flight muscle function, the nature of neuromuscular control of wing motion and its resulting importance to the aerodynamics of lift force production for weight support and thrust can be better understood. The results from these studies will be important for assessing the flight costs of birds under natural field conditions, for understanding muscle design in relation to the high mechanical power output required for flapping flight, and for determining whether novel lift generating mechanisms operate in birds which favor their ability to maneuver and modulate flight behavior in ways that are not possible for fixed-wing, human-engineered aircraft.

A grant has been awarded to Harvard University under the direction of Dr. George Lauder for the acquisition of a volumetric imaging system for the three-dimensional reconstruction of macroscopic fluid flows in organismic biology. The instrumentation will be shared among three cooperating institutions (Harvard, Brown University, and the University of Rhode Island) to: (1) analyze air flow patterns resulting from wing and body movements of flying bats and birds, (2) study water flow patterns in the wake of swimming fishes, (3) analyze water flow patterns during prey capture by small sharks, (4) study air flow over leaves and flowers of plants, and (5) measure unsteady pressure or shear-driven flows adjacent to flexible boundaries. The study of air and water flow patterns resulting from animal locomotion and prey capture is a major endeavor in the field of biomechanics. As animals capture prey and move through air and water, they generate complex three-dimensional patterns of fluid movement that reflect the application of force to the environment. Understanding these patterns of fluid movement is critical to uncovering the fluid dynamic mechanisms that govern flight, swimming, and the capture of prey by organisms living in fluids. Similarly, understanding the process of wind pollination in plants and the movement of air over leaves is dependent on quantification of air flow and measurement of air velocities around complex three-dimensional plant structures.

The instrumentation will benefit directly numerous graduate students currently in the laboratories of the major and minor user faculty by providing them with the latest technology for the study of biological fluid mechanics. Three of the major users teach advanced undergraduate research project classes in biomechanics (at two different institutions), and undergraduates doing projects in the area of biological fluid mechanics will have the opportunity to use this equipment as they participate in laboratory research projects.

This IGERT project is a multidisciplinary program of education and research focused on biomechanics. Biomechanics is the study of phenomena in biology that is broadly concerned with the mechanical characteristics of cells, tissues, and organs. It deals with both structural aspects - for example, the strength of the cytoskeleton and the Young's modulus of the cell - and dynamic aspects - the motion of fluids in biological microchannels and the action of biological micromotors. Understanding these phenomena and processes requires combining methods, tools, and styles of research from biological and physical sciences, and from engineering. The IGERT program is intended to offer Ph.D. students an education designed to make them proficient in the methods of both biological and physical sciences. The research component of the program will generate improved understanding of important and relatively unexplored biological processes; it will also use this understanding to design inanimate systems that mimic aspects of the biological systems (biomimetic systems). The educational component will combine thesis programs that require co-advisors from biological and physical science and engineering, research rotations through laboratories with different styles of research, and active interaction among students with different backgrounds. The program will support 10 students per year, and involve 20 faculty at Harvard in the departments of biology, chemistry, and physics, the Division of Applied Science and Engineering, and the Medical School. Many of these research groups already collaborate in other projects: the proposed program will strengthen and extend these collaborations, to the benefit of both students and faculty.

IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the multidisciplinary backgrounds and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing innovative new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. In the fifth year of the program, awards are being made to twenty-one institutions for programs that collectively span the areas of science and engineering supported by NSF.

[unreadable] DESCRIPTION (provided by applicant): The proposed research addresses the central question of how muscles function under dynamic conditions of locomotor activity. It does so in the context of how muscle function is modulated in relation to muscle architecture and fiber composition to accommodate changes in locomotor requirement. These questions will be addressed by making in vivo recordings of force (tendon buckle transducers), length change (sonomicrometry) and neural activation (electromyography) of key limb muscles in two animal models: quadrupedal goats and bipedal guinea fowl. Measurements will be obtained from animals trained to move over a range of speeds on a treadmill at different gaits and grades (level vs incline vs decline) to address the following hypotheses: (i) regional activation and fractional length change within muscles that have focal skeletal attachments is uniform both along a fascicle axis and between differing fascicle regions, but may vary in muscles with broader attachments and more complex architectures; as a result, (ii) the timing and strain of activated fascicles are homogeneous within a muscle performing a given motor task; and (iii) proximal muscles with long fibers account for the majority of mechanical work modulation; whereas distal short-fibered muscles with long tendons contract isometrically for more economical force production and tendon elastic savings. Differences in mechanical work rate with locomotor grade will be related to observed changes in the in vivo force-length behavior of key limb muscles. Recordings made while animals accelerate from rest will provide a second context to evaluate work modulation in relation to muscle architecture. Ground reaction force-platform and high-speed video recordings will also be carried out to integrate the in vivo force, length and EMG measurements of individual muscles into whole-limb mechanics. These studies have important consequences for understanding patterns of motor recruitment in relation to locomotor strategy and how regional differences in motor unit organization (and fiber type) may influence the neural control of movement. Prior work in this area has been limited by studies of motor function under more quasi-steady ranges of movement and/or indirect assessment of muscle length change and force development. Although an overarching goal is to understand factors that influence normal and age-related changes in human motor function, animal studies allow direct experimental approaches for assessing the dynamics of motor function that are likely to apply to humans. Consequently, the proposed studies will have value for developing more effective physical, occupational and rehabilitative therapies, as well as for sports and exercise training, and prosthetics design.

[unreadable] DESCRIPTION (provided by applicant): Neuromechanics is an inherently interdisciplinary field that combines approaches from neurobiology, organismal biology, engineering and computer science to understand the neural control of movement. The goal of this symposium is to bring together scientists from these diverse fields to explore the relationship between biomechanics and neural control of movement, to define general principles of neuromechanics, and to identify critical areas for future work. A second goal is to expose younger biological scientists to the opportunities and challenges of quantitative modeling and interdisciplinary research, as well as the need for bridging neuroscience and comparative biology with engineering and computer science. Historically, studies of the neural control of movement have developed mainly within the field of neuroscience. Over the past 25 years, however, the idea that the biomechanics of peripheral structures plays an important role in neural control has become increasingly well established. From a design perspective, it seems clear that algorithms for controlling a body must take into account the details of how that body works. However, our understanding of precisely how biomechanics influences neural control of movement is still rudimentary. A major challenge is the complex, multidimensional organization of animals and the non-linear properties of neurons and neuromotor circuits. A main theme of the symposium will be to understand how the dynamics and mechanics of body movement in relation to the physical environment are integrated with, and may help simplify, neural motor control. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The overarching goal of the proposed research is to improve the quality of understanding and assessment of neuromotor performance that can be obtained through the use of electromyographic (EMG) recordings of muscle activity patterns and Hill-type muscle models. Muscle modeling and EMG analysis has widespread use for improving the assessment and development of rehabilitation therapies important to the treatment of motor impairment, as well as changes in muscle function associated with aging. EMG recordings, whether from indwelling electrodes or measured from the skin surface, are frequently used in combination with muscle models to simulate and evaluate motor performance to address a broad range of clinical problems and therapies that include gait rehabilitation, the evaluation and treatment of stroke, wheel chair use, and prosthetics. This work seeks to combine cutting-edge basic science analysis of muscle properties and in vivo contractile function with computational muscle models for interpreting the contractile performance of whole muscles relative to their motor recruitment patterns. The proposed work is designed to directly test and refine the models, facilitating improvements to the quality of muscle modeling that can be applied in human neuromotor studies to a range of clinical problems and conditions. By combining direct in vivo recordings of muscle force (via tendon force buckles), fascicle length change (via sonomicrometry), and neural activation (via multiple indwelling fine-wire EMG electrodes) in an animal model (goat hind limb muscles), quantitative measures of in vivo contractile performance will be used to validate and improve the fit of four different Hill-type muscle models based on muscle activation and architecture. Spatio-temporal features of the EMG signals recorded within the muscles will be analyzed using wavelets to examine patterns of motor recruitment in relation to in vivo contractile performance of select muscles. These will be used to derive and test activation patterns used as input to the muscle models. Fundamental features, such as the Henneman size-principle for orderly recruitment and changes in work output (concentric versus eccentric exercise), will be examined to test and refine the models. Sensitivity analyses will also be carried out to test model output robustness against known changes in model input parameters derived from in situ muscle measurements of activation and force development rates, F-L properties, and Vmax. The following two specific aims will be examined: Aim #1 will examine the ability of different Hill-type muscle models to characterize measured patterns of whole muscle force and work output under in vivo conditions, based on activation input derived from the fine-wire EMG recordings. Time-frequency spectra of the EMGs will be analyzed to reveal patterns of motor unit recruitment, testing the hypotheses that: (a) differential patterns of motor recruitment (between the fast and slow units) occur during goat locomotion, and (b) the faster motor units are preferentially activated, relative to slow units, for tasks that require high strain rates and high rates of force development. Measurements of intrinsic in situ muscle properties, architecture and fiber type will also test the hypothesis that a homogeneous distribution of fiber types and pennation angle within muscle regions results in uniform patterns of fascicle strain and contractile function for a given type of locomotor behavior. Aim #2 will analyze detailed spatio-temporal features of the EMG recordings made within local muscle regions of select limb muscles using wavelets to provide a quantitative time-varying evaluation of motor unit recruitment. In situ recordings of twitch force development and slack-test releases will provide estimates of the intrinsic properties of the different motor units. Wavelet analysis will be used to refine and improve algorithms developed for the activation/deactivation dynamics used in the muscle models to improve their fit to direct measurements of muscle contractile performance. Aim #2 will test the hypothesis that the time-varying patterns of whole muscle force development are better predicted by muscle model that incorporate the actual in vivo motor recruitment patterns tha models that do not. PUBLIC HEALTH RELEVANCE: The relevance of the proposed research to public health is that it will help improve the clinical assessment of neuromotor performance that can be obtained through non-invasive use of electromyographic (EMG) recordings of patient muscle activity patterns associated with particular motor functions, such as gait or manipulation and grasping. EMG recordings are commonly made from surface (skin mounted) electrodes to assess neuromuscular function in an individual. These muscle activity recordings are then interpreted to assess and develop rehabilitation therapies, important to the treatment of motor impairment, such as that which results from stroke, as well as changes in muscle function associated with aging. Muscle researchers also widely use Hill-type muscle models derived from known physiological force-velocity and force-length properties of skeletal muscle to simulate or predict the motor output of a muscle based on its measured EMG activation. The combination of non-invasive EMG recordings as input to drive muscle models for predicting biomechanical outcomes is frequently used to address a broad range of clinical problems and therapies, including functional electrical stimulation, applied to gait rehabilitation, the evaluation and treatment of stroke, and prosthetics and orthotics. However, in humans, such models of an individual's muscles cannot be tested directly. Further, most muscle models assume uniform motor unit characteristics, whereas most muscles have mixed populations of motor units that can be differentially recruited. Consequently, the proposed work seeks to combine cutting-edge basic science analysis of muscle properties and in vivo contractile function, based on novel recording and analysis methods, with computational muscle models that will allow the models'output to be assessed directly by the measurements of the muscle's contractile performance in the living animal. Goat muscle function will be assessed across a range of physical activity using methods that allow muscle force, length change, and activation to be recorded in vivo. Wavelet decomposition of regional EMGs within the muscle will allow the recruitment patterns of motor units to be identified in relation to changes in contractile performance. The proposed work is designed to facilitate the refinement of Hill-type muscle models to improve their ability to predict muscle force and work output that can be obtained from non-invasive EMG recordings of muscle, which are commonly made in the clinical laboratory setting and applied to the assessment and treatment of broad range of motor disorders and conditions.

This project seeks to investigate the neuromuscular control of maneuvering flight in relation to wing and body movements and aerodynamic forces during turning in two bird species (pigeons and cockatiels). Understanding how birds control turning maneuvers will help to reveal how birds achieve stable movement, yet at the same time are highly maneuverable, compared to human-engineered fixed-wing aircraft. The project will therefore have broader relevance to the development of micro-air vehicles offering unmanned flight capability for surveillance and remote monitoring. The project also has relevance for understanding a critical component of a bird's flight ecology critical to their success. Past work has largely examined level flight at constant speeds, but little is known about other aspects of flight (ascent, descent, turning, take-off and landing). New techniques now enable direct measures of neuromuscular activity over a broader range of flight performance. These physiological and biomechanical techniques will measure muscle activity and length, synchronized with high-speed video recordings of body and wing movements. The project will have broad educational impact for students, as well as the public. Bird flight has captivated man for much of recorded history, motivating myths and inspiring the aeronautical engineering behind aircraft design. High-speed videos of bird maneuvering flight will have intrinsic appeal for revealing the complex and coordinated pattern of movement to the general public and students of all ages. The investigative team has worked with television studios (Discovery Channel, PBS) to bring the appeal and inspiration of biological flight to a broader audience. The investigative team also regularly hosts visits with school groups to observe its research on bird flight. The research will enhance the training of a PhD scientist and offer involvement of undergraduate and high school students who conduct research in the investigator's lab.