Ronald J. Triolo, Ph.D. - US grants

neuromuscular stimulator; paraplegia; clinical biomedical equipment; biomedical equipment development; medical implant science; human subject; clinical research;

[unreadable] DESCRIPTION (provided by applicant): The purpose of this study is to provide meaningful standing function to individuals with motor complete thoracic spinal cord injuries via a new 16-channel implanted neuroprosthesis, and quantify its clinical and technical benefits over existing 8-channel implanted systems. Standing function will be achieved in the home and community environments through continuous supramaximal activation of the trunk, hip and knee extensors along with selected ankle plantar/dorsiflexors and hip ab/adductors in an open-loop manner. The additional channels of stimulation afforded by the new implanted stimulator-telemeter will improve several clinically relevant measures of standing performance over currently available systems. In addition, we will develop a novel control system to automatically regulate posture and actively restore standing balance to individuals in the well-controlled laboratory environment. Thus, we will begin to address the shortcomings of all other implanted functional neuromuscular stimulation (FNS) systems for standing by developing a sensor- driven control system that will actively monitor posture, anticipate perturbations to balance and automatically modulate stimulation to keep the user upright. This will be accomplished by combining innovative feed- forward, feedback and predictive control elements in three dimensions and at multiple joints based on global variables derived from a small number of simple, but information-rich, body-mounted sensors. Dynamic stability will be achieved by using accelerations of the trunk to predict and rapidly respond to the anticipated effects of perturbations, while static stability will be achieved by regulating center of pressure within the base of support using feedback control. A model-based approach to controller development will be adopted that involves computer simulation and laboratory testing with recipients of the 16-channel implanted stimulation system. The ability of the new control system to perform in the presence of spasms and changing muscle properties due to fatigue, as well as its sensitivity to control parameter selection and sensor accuracy, will be evaluated in simulation. This new control system should reduce reliance on the upper extremities while standing with FNS in the laboratory, thereby advancing the goal of eventually providing neuroprosthesis users with freer use of their hands to manipulate objects in the environment by automatically maintaining balance in the presence of intrinsic and extrinsic disturbances. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The primary objective of this investigation is to address the limitations of currently available first generation functional electrical stimulation (FES) systems for standing after spinal cord injury by a) activating a greater portion of the targeted muscles to increase available knee extension moment and b) selectively recruiting synergistic muscles to offset fatigue. We will accomplish this through the innovative application of nerve-based cuff electrodes in a series of translational research studies designed to build upon existing animal work and safely and efficiently introduce them into human clinical trials. All current implanted FES systems for standing utilize muscle-based stimulating electrodes that only partially activate the available motor unit pool. While more than adequate for smaller and lighter implant recipients, this approach yields insufficient knee extension moment for heavier or taller candidates. Such individuals require more complete activation of the quadriceps to achieve acceptable functional standing, while simultaneously avoiding the counterproductive hip flexion caused by the femorally innervated sartorius and rectus femoris. The first goal of this study is to demonstrate the feasibility of utilizing stimulating nerve cuff electrodes in standing neuroprostheses, and thus extend the potential user population to individuals who currently cannot take advantage of the technology due to their size and weight. The proximal femoral nerve trunk is composed of numerous fascicles serving structures both advantageous and counterproductive to stable upright standing. Animal studies have demonstrated that a stimulating nerve cuff placing multiple contacts around the nerve can selectively activate individual fascicles within the nerve. The second goal of this investigation is to generate a realistic model of cuff-nerve geometry and determine the fascicular selectivity of multi-contact cuff electrodes on the multi-fascicular human femoral nerve via computer simulation analyses. This will result in an optimized cuff design that maximizes selectivity without detailed a prior knowledge, and thus suitable for clinical use. The third and final goal of this project is to establish the acute and chronic performance of multi-contact cuff electrodes in vivo in human volunteers. Intermittent and cyclic stimulation to individual contacts of chronically implanted electrodes on the distal peripheral nerve branches innervating the vastus lateralis and intermedius will allow fibers to rest while maintaining a constant net submaximal joint moment, effectively increasing duty cycle and allowing some recovery from fatigue. Selectivity of multi-contact nerve cuff electrodes on the proximal femoral nerve will be established in a series of acute intra-operative tests. Completion of this project will extend the functionality of existing neuroprostheses and provide immediate benefit to current system users. It will expand the potential user population, improve consistency of standing performance across individuals, and delay the effects of fatigue. Selective activation of individual muscles from a single multi-contact cuff electrode around a multi-fascicular nerve trunk will simplify the surgical installation of systems that provide more advanced functions such as stepping and stair climbing. Thus, in addition to their immediate impact on the functionality and performance of standing systems, the proposed studies will build a foundation for future developments in lower extremity neuroprostheses by selectively activating the appropriate fascicles in the proximal femoral nerve trunk.

implant; nervous system prosthesis; spinal cord injury; body movement; neuromuscular stimulator; paraplegia; medical implant science; human subject; clinical research;

neuromuscular stimulator; spinal cord injury; decubitus ulcer; paralysis; medical complication; assistive device /technology; neuromuscular disorder; clinical research; human subject;

DESCRIPTION (provided by applicant): This continuation of project EB001889 will extend the functional capabilities of recipients of implanted neuroprostheses for restoring lower extremity function after spinal cord injury (SCI) by applying new nerve cuff electrodes that selectively activate fascicles within the human femoral and sciatic nerves to isolate knee extension for standing, and both hip flexion and ankle plantar/dorsiflexion for efficient stepping. The new enabling technologies we will develop and deploy include the Compliant FINE (C-FINE), and an 8-channel nerve cuff module for the Networked Neuroprosthesis System (NNPS). The C-FINE offers distinct advantages over earlier nerve cuff designs, including a shape that matches the native nerve morphology, a contoured stiffness profile for flexibility along the nerve's length, an simple layered construction suitable for micro- fabrication of higher density contact arrays. This new neural interface will significantly simplify implant surgery and improve the performance of lower extremity neuroprostheses, while the new stimulation module for the NNPS will enable the realization of sophisticated systems employing multiple C-FINEs for advanced lower extremity functions. We will implant C-FINEs on the femoral nerves proximal to branching of the innervation to the sartorius and individual heads of the quadriceps in three new recipients of standing systems based on our existing 16- channel implanted stimulators (IST-16). We expect the superior selectivity of the C-FINE to allow independent activation of functionally distinct groups of axons innervating knee extensors and hip flexors. This should maintain or improve the standing performance achieved with other electrodes by increasing the available stimulated knee extension strength, while simultaneously providing access to the nerves that control the hip flexion required for reciprocal stepping. Active plantar/dorsiflexion with balanced inversion/eversion should also greatly improve the quality and speed of walking by injecting propulsive energy for forward progression, and enhancing foot-floor clearance of the swinging limb. We will implant C-FINEs on the tibial and fibular nerves above the knee in three additional subjects, and exploit their selectivity to produce strong ankle plantar/dorsiflexion with balanced inversion/eversion with the new NNPS system. The complex structure of the proximal sciatic nerve has prevented application of existing low-density nerve- based electrodes to the hamstring muscles, which are important for safe and standing and stepping. We expect that a single nerve cuff electrode with high number of contacts located on the proximal sciatic nerve will be able to isolate and fully activate the individual hamstrings to provide strong hip extensio and knee flexion. We will establish the feasibility of high density interfaces to the sciatic nerv in acute intraoperative tests, which will improve the performance and simplify the surgical implantation of future lower extremity neuroprostheses.

DESCRIPTION (provided by applicant): The goal of this project is to develop new control systems to restore standing function and enhance the postural stability of individuals paralyzed by spinal cord injuries (SCI). Systems that provide the ability to stand, alter standing posture, and maintain balance by automatically adjusting stimulation to the paralyzed muscles will be designed, optimized in simulation, and evaluated experimentally in six volunteers with SCI. The project will result in a unique, comprehensive balance control system that extends the capabilities and improves the safety of all currently available standing neuroprostheses. The first aim is to design, implement and test posture-follower and regional set-point control sub- systems. The posture-follower control element will automatically alter stimulation as users vary their standing postures about the nominal erect position by simply pulling or pushing against a walker. This will ensure that the optimal stimulation to support the body is applied continuously as the center of mass is smoothly relocated to a new location. The regional set-point control element will automatically adjust stimulation to resist disturbances and maintain balance based on joint angle position and center of mass acceleration. This sub-system will be optimized to span the entire base of support and sustain the desired posture defined by the posture-follower. These new control elements will be designed and evaluated individually in simulation, followed by laboratory demonstration and clinical assessment in volunteers with SCI. The sub-systems will then be integrated and compared to constant activation of the paralyzed muscles. The resulting controller should facilitate standing reach and other functional activities of daily living, require less upper extremity effort to maintain balance, resist larger applied perturbations, and be perceived as easier to use than conventional methods of standing. The second specific aim is to develop the capability to execute a reactive step. This new control element will automatically change foot position to expand the base of support sufficiently to remain standing in response to large, destabilizing disturbances. Work will begin by fully characterizing the electrically-induced flexion withdrawal reflex and evaluating its potential for generating a rapid change in foot placement. These data will be incorporated into computer simulations to identify an appropriate trigger and optimize patterns of stimulation to generate reproducible stepping motion. The resulting sub-system will take action if the applied perturbations exceed those effectively resisted by the set-point controller, and thus avoid impending falls. Effectiveness will be fully assessed in simulation and laboratory experiments involving application of repeatable external perturbations. Finally, all three sub-systems will be integrated into a comprehensive balance control system and thoroughly assessed with recipients of advanced surgically-implanted 16-channel stimulators.

Wearable exoskeletons are one of the primary advancements that help to alleviate the effects of spinal cord injury (SCI) including degenerative changes in organs of the body. Artificially stimulating the wearer's muscles to move his or her limbs has the additional benefit of maintaining musculature and improving circulation. The exoskeleton system developed in this project will use this "muscles first" approach with additional assistive power from electric motors on an as-needed basis. The major contribution of the project is that it will ensure stability of the person during standing and at normal walking speeds. The result will be that persons with SCI will be more comfortable standing and walking more erect and, therefore, be more socially engaged. The societal impact of this will be that persons with SCI will be better able to work and participate in social and leisure activities and in other behaviors associated with independent and productive lifestyles. In addition, Cleveland area high school students will be involved in the project and learn about human biomechanics and engineering methods.

This project addresses how cyber physical walking systems (CPWS) can be designed to be safe, secure, and resilient despite a variety of unanticipated disturbances and how real-time dynamic control and behavior adaptation can be achieved in a diversity of environments. Specifically, a CPWS will be developed that seamlessly integrates: (1) a person who has a spinal cord injury (SCI) with intact and excitable lower motor nerves; (2) an exoskeleton with controllably locked/unlocked and/or passively damped joints; (3) DC motors for need-dependent joint power assistance; and (4) computational algorithms that continuously and automatically learn to improve standing and walking stability. In this "muscles first" approach, functional neural stimulation (FNS) provides most of the joint torques for walking and for maximum health benefits and, thus, as-needed assistive joint motors may be small and lightweight. The specific aims are 1) Assist the user's muscles on an as-needed basis and for high-bandwidth stability control by adding small, low passive-resistance motor/transmission pairs to our CPWS; 2) Develop computational algorithms for system estimation, machine learning and stability control for SCI users standing and walking with a CPWS while minimizing upper extremity effort; 3) Verify system performance with able-bodied individuals and assess upper extremity reduction and balance control in individuals with SCI using the CPWS for standing and ambulation.

DESCRIPTION (provided by applicant): This continuation of project EB001889 will extend the functional capabilities of recipients of implanted neuroprostheses for restoring lower extremity function after spinal cord injury (SCI) by applying new nerve cuff electrodes that selectively activate fascicles within the human femoral and sciatic nerves to isolate knee extension for standing, and both hip flexion and ankle plantar/dorsiflexion for efficient stepping. The new enabling technologies we will develop and deploy include the Compliant FINE (C-FINE), and an 8-channel nerve cuff module for the Networked Neuroprosthesis System (NNPS). The C-FINE offers distinct advantages over earlier nerve cuff designs, including a shape that matches the native nerve morphology, a contoured stiffness profile for flexibility along the nerve's length, an simple layered construction suitable for micro- fabrication of higher density contact arrays. This new neural interface will significantly simplify implant surgery and improve the performance of lower extremity neuroprostheses, while the new stimulation module for the NNPS will enable the realization of sophisticated systems employing multiple C-FINEs for advanced lower extremity functions. We will implant C-FINEs on the femoral nerves proximal to branching of the innervation to the sartorius and individual heads of the quadriceps in three new recipients of standing systems based on our existing 16- channel implanted stimulators (IST-16). We expect the superior selectivity of the C-FINE to allow independent activation of functionally distinct groups of axons innervating knee extensors and hip flexors. This should maintain or improve the standing performance achieved with other electrodes by increasing the available stimulated knee extension strength, while simultaneously providing access to the nerves that control the hip flexion required for reciprocal stepping. Active plantar/dorsiflexion with balanced inversion/eversion should also greatly improve the quality and speed of walking by injecting propulsive energy for forward progression, and enhancing foot-floor clearance of the swinging limb. We will implant C-FINEs on the tibial and fibular nerves above the knee in three additional subjects, and exploit their selectivity to produce strong ankle plantar/dorsiflexion with balanced inversion/eversion with the new NNPS system. The complex structure of the proximal sciatic nerve has prevented application of existing low-density nerve- based electrodes to the hamstring muscles, which are important for safe and standing and stepping. We expect that a single nerve cuff electrode with high number of contacts located on the proximal sciatic nerve will be able to isolate and fully activate the individual hamstrings to provide strong hip extensio and knee flexion. We will establish the feasibility of high density interfaces to the sciatic nerv in acute intraoperative tests, which will improve the performance and simplify the surgical implantation of future lower extremity neuroprostheses.

PROJECT SUMMARY/ABSTRACT The overall goal of the proposed research is to develop new control systems to restore seated function and enhance the postural stability of the trunk for individuals paralyzed by spinal cord injury (SCI). Systems that provide persons with the ability to sit erect, alter their seated posture, and maintain balance by automatically adjusting stimulation to the paralyzed muscles will be designed, optimized in simulation, and evaluated experimentally in nine volunteers with SCI. The project will result in a unique, comprehensive trunk balance control system that extends the capabilities and improves the safety of all currently available trunk neuroprostheses. The first aim of the study is to design, deploy and test an advanced neuroprosthesis to stabilize the trunks of individuals with SCI and maintain upright sitting. A disturbance-rejection controller using information from body-mounted sensors will be optimized to maintain erect posture for disturbances in all directions around the seated user. In that way restrictive chest straps or custom seating adaptations are completely eliminated and the likelihood of falling from the wheelchair reduced to a minimum. The objective of the second aim is to tune, characterize and asses the performance of a system that will allow individuals with paraplegia to safely deploy their trunks and maintain the stability of non-erect postures, thus expanding their reachable workspace. Performance of this posture-changing controller will be determined in a series of experiments that deploy the trunk to different positions away from the backrest and testing the ability to remain steady at the desired postures. In the third aim, we will characterize the consistency, accuracy and fidelity of the implanted sensors in the new networked neuroprosthesis (NNPS). This will be done by collecting data in a series of experiments and developing an algorithm that will fuse the signals from the various sensors to produce a robust feedback signal suitable for control studies. Thereafter we will implement the disturbance-rejection and posture-changing control systems without external components with this new technology. This application addresses the main mission of the National Institutes of Health (NIH) to help lead the way toward important medical discoveries that improve people's health and save lives. In particular it coincides with the missions of NINDS to reduce the burden of neurological disease, NIBIB to improve health by leading the development and accelerating the application of biomedical technologies, and NCMRR to foster development of scientific knowledge needed to enhance the health, productivity, independence, and quality-of-life of people with disabilities.

The overall goal of the proposed research is to develop a new control system to maintain standing balance at various task-dependent, user-specified postures, and enable dynamically stable reciprocal stepping in persons paralyzed by spinal cord injuries (SCI) with an implanted motor system neuroprosthesis (NP) and prepare for ensuing home-going trials and clinical dissemination. A system that automatically modulate neural stimulation to maintain standing balance and generate successive reactive steps to achieve effective reciprocal gait will be translated to the Networked Neural Prosthesis System (NNPS). Each module of the NNPS contains internal sensors that would eliminate the need for external devices and cabling. The project will determine the feasibility of a safe and functional LE motor system NP that can be realized with a fully implantable system suitable for home and community use. Aim 1 will determine effective and efficient methods to estimate whole body center of mass (CoM) kinematics and evaluate suitability for real-time control with the NNPS. This will entail estimating CoM from external sensors attached to able-bodied volunteers and current recipients of standing and stepping NPs at the anticipated surgical location of modules of the NNPS. We will implement our existing biologically-inspired standing balance and stepping controllers with NNPS simulated signals in volunteers with SCI and evaluate their performance in response to internally generated and externally applied disturbances. Aim 2 will extend the control system to automatically generate successive reactive steps, and enhance inter-limb loading and dynamic balance during stance phases of gait. A system that enables forward progression of the CoM to maintain balance in the medio-lateral direction, optimizes forward propulsion, and ensures proper swing limb foot placement during successive reactive steps will be developed in simulation, and experimentally validated with able-bodied volunteers and recipients of implanted NPs. Our existing control systems for bipedal stance and reactive stepping will be adapted to maintain balance and achieve smooth translation of CoM during walking and recent development in the field of walking robots will be applied. We expect that walking with the extended biologically-inspired control system will be smoother, more efficient and more resilient to potential destabilizing influences than conventional pre-programmed stimulation. Aim 3 will create the resources required to translate the standing and walking controllers to the new NNPS platform in preparation for clinical implementation and ensuing home-going trials. Work will develop, document and verify operation of lower extremity-specific software and clinical/user interfaces to the NNPS. We will prepare and submit an Investigation Device Exemption to the USFDA for a new feasibility study of LE applications of the NNPS in preparation for ensuing clinical trials of safety and effectiveness.

7. Project Summary/Abstract The missions of this longstanding Training Grant are to provide training in musculoskeletal research to academically gifted individuals at the predoctoral and postdoctoral level and to develop these individuals towards productive careers in musculoskeletal research. The strong interdisciplinary nature of musculoskeletal research at CWRU provides an ideal framework for developing the trainees? research expertise as well as their appreciation for the importance of interdisciplinary approaches and their interest in musculoskeletal diseases. The faculty are highly collaborative and interactive and include 21 Training Mentors plus 13 Associate Mentors from fourteen departments in the School of Medicine, the School of Engineering, the College of Arts and Sciences, and the Cleveland Clinic Lerner Research Institute. There is a healthy mixture of biological-, engineering-, and clinical-oriented trainers, further emphasizing the importance of interdisciplinary approaches. Training is provided for two or three years to 4 predoctoral and 3 postdoctoral trainees per year. These outstanding individuals are identified by a careful, multi-step selection process. Training occurs through intensive participation in research projects as well as through a rigorous curriculum of courses, seminar, and conferences. The Director and Co-Directors are assisted by a Steering Committee and an Advisory Committee that formally review the overall program as well as the progress of each trainee on a regular basis. The success of the program is best appreciated by considering the career trajectories of our former trainees. 22 of them have obtained faculty positions at universities across the country and thirteen have developed federally-funded research programs. An additional nine current and recent trainees are in various stages of their continued training and plan research careers. Moreover, 79% of the trainees from the previous two funding periods are actively engaged in biomedical research/academics. Training future musculoskeletal researchers is crucial since musculoskeletal diseases are major causes of morbidity, mortality, and impaired quality of life for millions of people in the United States and the number of affected individuals will continue to increase in frequency as our population ages.