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Bone Quality: A Composite of Complex Phenotypic Traits

Funding Agency: National Institute on Aging
PI: Neil Sharkey
Other Investigators: Gerald McLearn, George Vogler and David Vandenbergh

Bone quality, defined here as bone’s inherent ability to resist fracture, can be viewed as a composite of phenotypic traits, each under polygenic and environmental regulation. The principal goal of this study is to positively identify chromosomal regions (known as quantitative trait loci or QTLs) that contain genes influencing skeletal strength and architecture (i.e. bone quality). Our over-riding hypothesis is that the mammalian genome contains several unknown or unconfirmed QTLs that profoundly influence bone quality. Furthermore, the effects of these QTLs, acting in concert with each other and the environment, are expressed in an age and sex dependent manner. We expect that different QTLs will exert influence on skeletal characteristics at different times over the lifespan, and that QTL expression will differ between male and female mice. We also expect that many QTLs act on bone through indirect physiologic pathways, which to date have been largely overlooked in the genetic literature. This longitudinal study will set the stage for future work employing QTL-based selective breeding. Our long-term goal is to elucidate the causal fields (created by genes, environment, gene-gene, and gene-environment interactions) that ultimately dictate the quality of our bones in old age. This is a collaborative project between investigators at CELOS and others at the Center for Developmental and Health Genetics.

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Optimizing Tendon Transfer Surgery for Hindfoot Varus in a Dynamic Cadaver Model

Funding Agency: Intramural/Pending
PI: Neil Sharkey
Other Investigators: Steve Piazza, John Challis

Dynamic varus of the foot due to cerebral palsy (CP) or cerebrovascular accident (CVA) is often treated by surgically manipulating musculotendinous structures to reduce the deforming force or render it more functional. Many different motor deficits can produce varus and several surgical procedures have been proposed for correction. However, current outcome data are difficult to evaluate, and there is little agreement about the relative merits of alternative procedures. The goal of these biomechanical studies is to compare the efficacy of several different tendon transfer procedures designed to correct dynamic hindfoot varus. These studies are part of ongoing work using a well-established dynamic cadaver model of human locomotion. The model allows for accurate simulation of neuromuscular dysfunction and enables precise comparison of different surgical corrections.

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Bone Strain, Fatigue Damage and Stress Fractures

Funding Agency: Intramural and Private Sources
PI: Neil Sharkey

We have several ongoing studies exploring the internal biomechanics of the foot and ankle. Many of these studies are aimed at examining the tissue-level mechanical effects of various interventions and surgical procedures. Bone strain, as it relates to tibial and metatarsal stress fracture, are particular areas of focus. Functional issues related to the plantar fascia and other soft-tissues structures of the foot are also under investigation.

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Total Ankle Arthroplasty

Funding Agency: Interdisciplinary Train Grant National Institute on Aging
PI: Neil Sharkey
Other Investigators: James Michelson

Total ankle arthroplasty (TAA) is a procedure aimed at improving the lives of people with disabling ankle conditions by replacing the damaged joint with a prosthetic implant. At this point in time, the success of TAA remains questionable; hence many surgeons opt for arthrodesis (ankle fixation) rather than arthroplasty. A variety of problems can be attributed to the disappointing record of TAA, including improper wound healing, aseptic loosening, misalignment, and limited range of motion. The overall objective of the proposed work is to develop an evidence-based design for a new TAA system that includes a simple, step-by-step surgical procedure for the proper implantation of the components. The study includes a detailed examination of the bony surfaces of the tibia and talus to characterize the geometry and planar orientation of the talocrural joint surfaces with respect to specific anatomical reference points. Anatomical geometry will be used to design surgical jigs and instruments to enable proper cuts and precisely align the components according to a unique, new method of lateral surgical implantation that is to be developed. The ultimate goal of this research is to develop a novel TAA system that will be easier to utilize than current TAA methodology, improve the overall results of the procedure, and enhance the quality of life of those suffering from acute ankle pathology.

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Musculoskeletal Computer Modeling of Foot and Ankle Disorders

Funding Agency: National Science Foundation (CAREER)
PI: Stephen Piazza
Other Investigators: Paul Juliano (Hershey Medical Center), James O. Sanders (Erie Shriners), Neil Sharkey, Peter Cavanagh (Cleveland Clinic Foundation)

The foot and ankle are two of the least well-understood areas of the human musculoskeletal system, in part because axes of joint rotation are difficult to define and have been shown to vary considerably during movement and between subjects. The lack of practical and accurate techniques for quantifying foot and ankle kinematics has led the mechanical analysis of the foot and ankle to lag behind that of other joints. This deficiency of mechanical understanding is disturbing because injuries and musculoskeletal disorders of the foot and ankle outnumber those seen at any other joint, especially among the elderly. This research addresses these problems by developing and refining computational tools that will be used to locate the two major joint axes of the ankle non-invasively in individual subjects through mathematical optimization techniques. In addition, we will create a collection of subject-specific graphical computer models based on MR scans of the lower legs of fifteen subjects and the resulting predictions of muscle function will be tested experimentally. These models will permit an orthopaedic surgeon to study the effects of an untested variation in a surgical procedure while minimizing the risks to actual patients.

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Changes in Muscle Moment Arms Induced by Split Tendon Transfer

Funding Agency: Whitaker Foundation
PI: Stephen Piazza
Other Investigators: Neil Sharkey, James O. Sanders (Erie Shriners)

Spastic equinovarus is a gait deformity that occurs frequently in cases of cerebral palsy, stroke, and brain injury. Overactivity in the muscles that invert the foot causes patients with this condition to walk in an unstable manner and predisposes these patients to painful bony deformities and muscle contractures. Successful treatment of equinovarus usually requires surgical correction, and split tendon transfers are the procedures most often performed to correct its varus component. Although these procedures dramatically alter the actions of muscles, their specific effects on joint mechanics are not well understood. Several variations on the procedures have been proposed to improve postoperative function or limit surgical exposure, but their mechanical effects are presently unknown. This research involves the application of established techniques for measurement of muscle moment arms in cadaver specimens utilizing a novel arrangement for variation of tendon tensions that will be used to characterize the mechanics of split tendon transfer and several of its variations. The results of this work may be used to improve different split tendon transfers that have been proposed to correct musculoskeletal problems other than equinovarus, and this study may lead to the development of new surgical techniques for the correction of equinovarus and other conditions.

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Computational Modeling of Total Knee Replacement Motions

Funding Agency: Stryker Howmedica Osteonics Inc.; Gerontology Center (PSU); Other sources pending
PI: Stephen Piazza
Other Investigators: Darryl D'Lima (Scripps Clinic)

This research focus on the development and evaluation of novel computational tools for the assessment of knee joint function following arthroplasty. Tools currently available for the evaluation of knee replacement designs include finite element analysis, wear simulators, cadaver tests, and CAD-based analyses. Clinical outcome studies, in vivo imaging, and retrieval studies all assess in vivo function but require implantation in actual patients and substantial amounts of time. Adequate range of motion is a critical component of successful clinical outcome, especially since total knee replacement is being performed on increasingly younger patients who expect to be more active. Range of motion may be limited by the implants themselves, by soft tissue tightness, or by impingement of the implants on the surrounding bone. These limitations are difficult to assess using cadaver models or in vivo measurements because of difficulties inherent in measuring soft tissue tensions and contact forces. Knee replacement is sometimes described as a _soft-tissue procedure_because of the challenges faced by surgeons in soft tissue balancing to produce a result that is neither too lax nor too tight. This work involves the creation of specimen-specific models based on musculoskeletal properties measured in individual cadavers. In vitro experiments will provide data for testing of the model predictions.

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Energy Storage in the Prostheses of Transtibial Amputees

Funding Agency: Pending
PI: Stephen Piazza
Other Investigators: None

Below-knee prostheses are often evaluated by examining the "ankle" joint power despite the fact that no such joint is incorporated into the design. Because energy can be stored in the prosthesis without deformation at the "ankle", comparisons to the ankle power curves of intact limbs may be lacking. This work involves (1) the application of musculoskeletal modeling techniques to evaluate the work done on the lower portion of the shank and the foot by muscles and reaction forces and moments carried by the tibia and fibula; and (2) the measurement of energy stored in the prostheses of transtibial amputees. This project will result in a better understanding of the energetics of prosthetics limbs and meaningful points of comparison for energetic measurements made in the clinic.

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Sensory Control of Multijoint Reaching:

PI: Robert Sainburg

The aim of this research program is to discern the neural mechanisms underlying control of multijoint reaching movements in humans. We combine both psychophysical experiments and biomechanical simulations to determine the neural processes underlying control of the complex mechanics of the musculoskeletal system. Because of such dynamics, the relationships between muscle activation and movement kinematics are complex and non-linear. Studies in proprioceptively deafferented patients, who lack sense of joint position and movement, have allowed us to examine the role of different types of sensory information in controlling intersegmental coupling forces (Sainburg et al., 1993, 1995; Ghez and Sainburg, 1995). More recent work, in neurologically intact subjects, has confirmed that the nervous system uses sensory information to develop transient representations, or internal models, of musculoskeletal dynamics, in accord with task specific constraints (Sainburg, Kalakanis, and Ghez, 1999). Computer simulations suggest that such representations are utilized to take advantage of specific mechanical properties of the limb during movement planning (Kalakanis and Sainburg, 1999). Recent findings (Sainburg et. al., 2002; Lateiner et. al., submitted; Brown et al., in revision) suggest that vision and proprioception contribute differentially to the movement planning process. Whereas, accurate proprioceptive information is critical for specifying initial limb conditions, visual information is employed, almost exclusively, for specifying movement direction. In addition, our findings provide further support for the idea that direction and distance are specified through independent neural channels.

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The Neural Foundations of Handedness: Evidence for Dynamic Dominance

PI: Robert Sainburg

Recent findings from our laboratory have revealed substantial differences in coordination between the dominant and non-dominant arms in healthy individuals. Such coordination asymmetries have previously been hypothesized to emerge from differential contributions of each cerebral hemisphere to unilateral arm movements. Indeed, the idea that both hemispheres contribute to unilateral arm movements is well supported by neural activation studies (Kim et al., 1993; Kawashima et al., 1998), as well as previous studies demonstrating motor deficits in the ipsilesional limb of stroke patients (Haaland and Delaney, 1981; Haaland and Harrington, 1994, 1996, 1999; Winstein and Pohl, 1995; Wyke, 1967). It has previously been proposed that the individual contributions of the left and right hemisphere to arm movements reflect the employment of feedforward, and feedback processes, respectively (Haaland and Harrington, 1994, 1996, 1999; Winstein and Pohl, 1995) However, based on our recent findings, we have proposed the dynamic dominance hypothesis, which attributes to the left hemisphere, control of limb and task dynamics, and to the right hemisphere, control of limb stiffness, largely determining the final position of reaching. This hypothesis has been supported by studies that have examined interlimb differences in multijoint reaching (Sainburg and Kalakanis, 2000; Sainburg 2002; Bagesteiro and Sainburg, 2002a), targeted single joint movements (Bagesteiro and Sainburg, 2002b), and studies examining transfer of learning between the limbs (Sainburg and Wang, 2002; Wang and Sainburg, 2003). In contrast to previous hypotheses, we expect that both controllers mediate both feedforward and feedback processes, but that the quality of those processes depends on the characteristics of each controller. In support of our hypothesis, Prestopnik et al., (2002) have reported that patients with left hemisphere stroke show deficits in trajectory control, whereas patients with right hemisphere lesions show deficits in final position accuracy. We expect that further research will provide the link between the feedback/feedforward hypothesis and the dynamic dominance hypothesis of motor lateralization.

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Mechanisms Underlying Interlimb Transfer of Motor Learning

PI: Robert Sainburg

The tendency for practice of a novel activity with one arm to affect subsequent performance with the other arm has previously been demonstrated for a number of tasks, such as finger tapping (Laszlo, Gaguley, and Bairstow ,1970), keyboard pressing (Taylor and Heilman ,1980), inverted and/or reversed writing (Parlow and Kinsbourne, 1989; 1990; Latash, 1999), figure drawing (Thut et al. 1996), and reaching during coriolis force perturbations (DiZio and Lackner, 1995), and during visuomotor displacements (Elliot and Roy, 1981; Imamizu and Shimojo, 1995). However, the mechanisms underlying this transfer are not well understood. Intermanual transfer of motor adaptation is thought to reflect the sharing of specific learned information between left and right arm control systems. Recent findings from our laboratory support the idea that initial training with one arm can improve subsequent adaptation with the other arm. However, different aspects of control appear to transfer in different directions: Opposite arm training improves the initial direction of dominant arm movements, whereas it only improves the final position accuracy of non-dominant arm movements. This suggests that the direction of transfer depends on the proficiency of the arm controller in question for specifying particular features of movement. Current studies suggest that other types of learning transfer differentially, such that adaptation to novel inertial loads transfers from the dominant to the nondominant arm. The mechanisms of this transfer are currently being probed.

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Differential Contributions of Left and Right Hemisphere to Unilateral Reaching

PI: Robert Sainburg

Data from the National Heart, Lung, and Blood institute indicate that about 600,000 people in the US suffer from stroke each year, and incidence doubles for each decade of life after age 55 (AHA, 2002). About 4.5 million stroke survivors are alive today, which makes the long term functional impact of stroke a significant public health concern. The majority of strokes resulting in motor deficits can be characterized as unilateral, with the most severe impairment restricted to one side of the body. The focus of motor rehabilitation after stroke has traditionally been the limb contralateral to the damage. However, deficits have previously been identified in the ipsilesional limbs (Ref. 6-10, 19, 20). Because functional recovery is largely based on the coordinated use of the ipsilesional limb, understanding these deficits is imperative for optimal rehabilitation. A major goal of the proposed studies is, thus, to increase our understanding of the functional capacities and deficits in the ipsilesional arm, following unilateral brain damage due to stroke.

The idea that both hemispheres contribute to unilateral arm movements is well supported by neural activation studies (Kim et al., 1993; Kawashima et al., 1998), as well as previous studies demonstrating motor deficits in the ipsilesional limb of stroke patients (Haaland and Delaney, 1981; Haaland and Harrington, 1994, 1996, 1999; Winstein and Pohl, 1995; Wyke, 1967). The purpose of this line of research is to comprehensively examine the coordination deficits in the ipsilesional arm, following unihemispheric brain damage due to stroke. We employ experimental paradigms that have previously demonstrated differences in dominant and non-dominant coordination in healthy subjects Sainburg and Kalakanis, 2000; Sainburg 2002; Bagesteiro and Sainburg, 2002; Sainburg and Wang, 2002; Wang and Sainburg, 2003). In these multidirection reaching tasks, inverse dynamic analysis of segment torques, as well as, electromyography is employed to compare differences in trajectory dynamics. Through these studies, we hope to better characterize the motor capacities and impairments in the ipsilesional arm of unilateral lesioned stroke patients. We also hope to better understand the individual contributions of each hemisphere to control of unilateral arm movements.

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Modeling Sit-to-Stand in the Elderly

Funding Agency: The Whitaker Foundation
PI: John H. Challis
Other Investigators: Neil Sharkey, H.J. Sommer

Rising from a chair is clearly a precursor to gait and therefore is a significant determinant of independence, yet more than two million people in the United States over the age of 64 years have difficulty in performing sit-to-stand (STS). The purpose of this project is to examine STS in the elderly. The project combines experimental and computer simulation work to examine performance of sit-to-stand in the elderly. It is anticipated that this project will permit a better understanding of the objectives being met when performing STS, provide insight into the potential limiting factors for the elderly performing this task, and thus give guidance for the design of programs to ensure maintenance of this ability.

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Wobbling Mass Influences on Human Movement

Funding Agency: Intramural
PI: John H. Challis
Other Investigators: M.T.G.

Pain Human movement is typically punctuated by a series of impacts, for example heel strike during gait. Evidence from animal studies has shown that repeated high impulsive loadings can produce degenerative changes in cartilage; therefore during gait the dissipation of the energy associated with the impact can be very important. The major hypothesis of this project is that the motion of the soft tissue of the shank makes a significant contribution to the dissipation of the energy associated with impacts during gait. It is anticipated that the soft tissue motion will reduce ground reaction forces due to some of the energy of impact being transferred to the soft tissue of the shank. The series of planned studies should permit detailed elucidation of the role of the motion of the soft tissue of the shank in the dissipation of energy during impacts.

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Tendon Properties in vivo

Funding Agency: Industry
PI: John H. Challis

Tendons have elastic properties which have important implications for both the energetics and control of human movement. Tendon cross-sectional area and strain can be estimated using ultrasound imaging. The purpose of this study is to examine how tendon properties of the triceps surae change as a consequence of aging, and how these changes may influence movement. Tendon properties are measured using ultrasound, and given these measured properties simulation models are used to examine the implications of these properties on the energetics and control of human movement.

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Prehension Synergies

Funding Agency: NIH
PI: Vladimir Zatsiorsky, Ph.D.
Investigator: Mark L. Latash, Ph.D.

Deterioration of hand function with age and with a variety of neurological and peripheral disorders is a major challenge for the area of motor rehabilitation. We think that progress in this area has been relatively slow because of poor understanding of how the digits of the hand are coordinated in everyday tasks. A major long-term objective of this line of research is to overcome this deficiency and move closer to making recommendations regarding optimization of current hand rehabilitation approaches.

Two considerations inspired the study. Firstly, the study of hand and finger function has potentially many applications ranging from hand clinics to robotics. Secondly, from a more theoretical perspective, prehension constitutes a convenient model for studying the problem of motor redundancy. Manipulation of hand-held tools in three-dimensional space is a complex task. At the contact points, each finger exerts three force components and three moment components. Hence, five fingers exert collectively 30 force and moment components. The weight, static moment and moment of inertia of the hand-held object also contribute to the task complexity. The number of mechanical parameters that have to be recorded in such an experiment easily exceeds 50. This itself makes experimental research difficult. In multi-finger grasps, the fingers are statically redundant—the number of unknown forces exceeds the number of equilibrium equations—and kinematically over-constrained, a variation in the position of a grasped object affects the position of all the fingers. When a task is to produce a certain mechanical effect by activating several fingers, e.g. to generate a required torque and/or force, the effort can be distributed among the involved fingers in many different ways. Conceptually, the problem is similar to the distribution of force among the muscles serving a joint. The study of force distribution among fingers is advantageous because the finger forces can be measured directly and, consequently, the validity of models and hypotheses can be readily scrutinized.