Robert F. Kirsch - US grants

DESCRIPTION (Adapted from the Applicant's Abstract): This study will implement, evaluate, and optimize a neuroprosthesis based on functional neuromuscular stimulation (FNS) which will restore shoulder function to spinal cord injured individuals with C5 tetraplegia. Such individuals retain little or no voluntary control over motions acting to move the upper arm toward the midline, due primarily to paralysis of the pectoralis major (PM) and latissimus dorsi (LD) muscles. This loss of control significantly reduces the range of motion of the hand, excluding an important workspace volume near the midline, and prevents arm stabilization in the natural abducted postures used in many tasks like eating and writing. Restoration of these functions would significantly improve the independence of these individuals in a number of daily activities, improving their quality of life and reducing their attendant care costs. The main hypothesis of this study is that FNS of a small number of sites in the PM and LD muscles can significantly improve shoulder function in horizontal flexion, adduction, and internal rotation in individuals with C5 tetraplegia. The stimulated contractions will restore the lost motions, while retained voluntary control of antagonistic muscles will be used by the individual to overcome the stimulated contractions and achieve intermediate positions and external forces in a completely natural manner. After verifying the hypothesis that individuals with a C5 Function level retain sufficient stimulated strength in the PM and LD and adequate voluntary control over their antagonists, experiments will test the hypotheses that the shoulder neuroprosthesis expands the workspace volume accessible to the hand, improves postural stability, and allows more rapid and accurate arm movements. Several general methods for improving control of the partially paralyzed shoulder will also be developed. Shoulder stiffness properties will be used to identify deficits in postural stability in a systematic manner and to suggest changes in electrical stimulation patterns to correct the deficits. The feasibility of using electromyographic recordings from voluntarily-controlled shoulder muscles to modulate stimulation of the paralyzed muscles will be investigated, since such modulation could improve movement performance, prevent fatigue, and compensate for changes in contraction strength in different shoulder positions.

The proposed study will examine several important issues which must be addressed in order to restore movements involving the wrist, elbow, and shoulder joints in C4-C7 quadriplegics using electrical stimulation of the muscles acting at these joints. The first issue that the mechanical effects (e.g., force) produced by the individual stimulation of each muscle acting at these joints must be known. A robotic manipulator will be used to experimentally determine the force and impedance components produced at the hand by individual paralyzed muscles for different levels of stimulation intensity and for various hand locations in space. The second issue to be addressed is how to best select a combination of muscles to stimulate to restore a specified task, since different combinations of muscles can often achieve the same behavior. The third issue to be addressed is how to specify desirable mechanical properties for movements to be restored by electrical stimulation.

This Integrative Graduate Education and Research Training (IGERT) award supports the establishment of a multidisciplinary graduate training program of education and research merging four existing research groups into a new entity with broad technical expertise yet still sharing a focus on Neuro-mechanical systems. Each existing group has a history of collaboration between various engineering fields and the biological sciences. However, meaningful interactions only came after considerable effort to overcome barriers. The training program will provide a formal process to help graduate students proceed through that process quickly and efficiently. Students in the training program will participate in cross-disciplinary courses and rotate through laboratories in all four fields. A multidisciplinary seminar featuring extended visits from leaders in each field will draw students together. Funds will permit travel to scientific meetings and workshops in each field. A common computer facility and office area will maintain interactions beyond the classroom. Internships in clinical and industrial settings will also be available as options. We have also planned an aggressive recruitment program emphasizing institutions committed to training students in underrepresented groups. Our trainees will graduate with appropriate tools and background necessary to work efficiently in teams. We believe that such an experience will pay great dividends to both the students and the disciplines in which they choose to work.

IGERT is an NSF-wide program intended to facilitate the establishment of innovative, research-based graduate programs that will train a diverse group of scientists and engineers to be well-prepared to take advantage of a broad spectrum of career options. IGERT provides doctoral institutions with an opportunity to develop new, well-focussed multidisciplinary graduate programs that transcend organizational boundaries and unite faculty from several departments or institutions to establish a highly interactive, collaborative environment for both training and research. In this second year of the program, awards are being made to twenty-one institutions for programs that collectively span all areas of science and engineering supported by NSF. This specific award is supported by funds from the Directorates for Biological Sciences, for Engineering, for Computer and Information Science and Engineering, and for Education and Human Resources.

[unreadable] DESCRIPTION (provided by applicant): This proposal seeks sponsorship for a 2 day workshop that will pull together experts from a range of disciplines to develop consensus design specifications for brain controlled rehabilitation systems such as functional electrical stimulation (FES)-based neuroprostheses for restoring upper extremity movement control to individuals with neurological disorders such as cervical spinal cord injury (SCI) and stroke. The goals of the workshop are to identify scientific and technological challenges that hinder the use of brain-machine interfaces (BMI) in clinically deployed rehabilitation systems and to suggest future research activities that would address these challenges. We will bring together experts from several different research areas (both natural and artificial control systems, neuroscience related to BMI, implanted BMI devices, and clinical applications) that may not typically interact but whose skills and insight are needed to develop an integrated approach to clinically relevant BMI's. The proposed workshop will include brief presentations by acknowledged experts in the various research areas and ample discussion on the individual topics presented by these experts. Workshop participants will be divided into five different Task Groups to identify challenges and suggest approaches in different areas: (1) Peripheral motor control considerations, (2) Sources and properties of available BMI signals, (3) Extraction of relevant movement control information from BMI signals, (4) Practical BMI devices, and (5) Clinical applications of BMI. The Task Groups will be asked to identify strategic research areas for moving BMI's into incrementally more sophisticated clinical applications over the next 1, 5, and 10 years. A summary report of these discussions and recommendations will be provided to NINDS following the meeting and published in an appropriate journal. PUBLIC HEALTH RELEVANCE: This proposal seeks sponsorship for a 2 day workshop that will pull together experts from a range of disciplines to develop consensus design specifications for brain controlled rehabilitation systems. The goals are to identify scientific and technological challenges that hinder the use of brain-machine interfaces (BMI) in clinically-deployed rehabilitation systems and to suggest future research activities that would address these challenges. A summary report of these discussions and recommendations will be provided to NINDS following the meeting and published in an appropriate journal. [unreadable] [unreadable] [unreadable]

Development of prototype control system that utilizes cortical signals to activate an external Funtional Electrical Stimulation , FES, controller to facilitate the movement of upper limbs in spinal cord injured patients. It is anticipated that the system developed will use functional brain signals to stimulate muscles for complex coordinated function, in assistive technology.

DESCRIPTION (provided by applicant): This proposal describes our Integrated Engineering and Rehabilitation Training program that produces biomedical Ph.D. graduates who combine state-of-the-art expertise in neural engineering (an area of biomedical engineering) with a genuine appreciation of the practice and challenges of clinical rehabilitation. This program is centered in the Department of Biomedical Engineering at Case Western Reserve University, but also includes the strong participation of several of our local medical centers. Our program is focused exclusively on predoctoral training and we have trained 37 students since 1999. We are requesting funding for a total of 8 training positions per year for five years. Trainees are typicaly funded by the program for two years each, so we expect to train a total of 20 BME Ph.D. students over the proposed 5 years. Trainees enter with undergraduate training in engineering or a closely related discipline (e.g., physics). They satisfy the rigorous requirements of the BME Ph.D. program and benefit from its existing features, while our T32 program adds value through highly collaborative and interdisciplinary research projects, a clinical immersion experience, and unique access to visiting seminar speakers (including a journal club). Over the next 5 years, we will add a formal course on Career Development for Neural Engineers, include a seminar series on diversity and formal diversity training, and form an external Advisory Committee comprised of academic leaders in rehabilitation and neural engineering, representatives of large and small companies in the stimulation and rehabilitation commercial space, practicing neural/rehabilitation physicians, and a student diversity professional. The specific objectives of our training program are: (1) Prepare our trainees for productive careers in rehabilitation and neural engineering; (2) Provide a rigorous engineering education that forms the basis for future innovation; (3) Provide specific expertise in the development and application of neural stimulation and complementary interventions for overcoming neurological disorders; (4) Provide specific expertise in modeling and simulation (musculoskeletal and/or neural); (5) Provide an extensive, hands-on clinical immersion experience that prepares each trainee for a translational career; and (6) Provide real-world professional development training to enhance post-graduation success. We have assembled a distinguished group of mentors who serve in one of three roles: Research Training mentors (14) who are the primary research advisors of the trainees, Associate Research Training Mentors (7) who are content experts on T32 trainee committees, and Clinical Training Mentors (14) from rehabilitation and surgical disciplines who insure the clinical relevance of each trainee research project. Trainee project topics include electrode development; stimulation pattern design; neural motor control mechanisms; neural biomaterials, protection, and repair; deployment of interventions to individuals with neurological disorders; neuroreahabilitation; modeling and simulation; and brain-computer interfacing.

We will deploy 4 new upper extremity neuroprostheses covering all elvels of cervical level spinal cord injuries (SCI) with sufficient numbers of subjects to provide support for larger clinical trials in the future. All of these neuroprostheses will use implanted stimulators and 3 of 4 2ill use implanted EMG recording modules. EMG-based control algorithms will provide fully implanted coman and control interfaces while exploiting the subjects'retained voluntary function. Both stimulation and recording odules will be commercially manufactured, greatly facilitating their eventual deployment in to the general clinical environment. This project will also push the frontiers of neuroprostheses in several significant ways. In collaboration with a parallel effort funded by NICHD, we will work to more "brain achine interfaces" into use as a neuroprosthesis command interface for individuals with high cervical spinal cord injusries. We will also examine the potential of useing the Flat Interface Nerve Interface (FINE) to activvate multiple muscles from as proximal a location as possible, potentially leading to a nerve electrode-only implementation with a lower surgical impact. Finally, we will examine the use of the FINE as an interface for recording from cutaneous enrve fascicles arising in the hand as a source of information for providing electrocutaneous feedback regarding the state of the hand.

The goal of this contract is to develop a prototype for an external Functional Electrical Stimulation (FES) control system that will restore function to one or more movements in paralyzed upper limbs of individuals with high level cervical spinal cord injury or individuals with appropriate forms of brain stem stroke.

This project will restore arm and hand function to individuals with complete paralysis using functional electrical stimulation (FES) AND will give these people the ability to command these movements in an effective and intuitive way using an intracortical brain-machine interface (BMI). We will use percutaneous interfaces for both the FES and BMI components to implement a fully functional but also reversible BMI-commanded FES system. This is the immediate next step in the ultimate realization of a permanently implanted BMI-controlled FES system. Paralyzed muscles of 5 individuals with high level (C1-C4) spinal cord injuries will be implanted with FES electrodes to restore multiple motions of the arm and hand sufficient for meaningful multi-joint, functional activities. In the same individuals, a 96-channel intracortical array (BrainGate2) will be implanted in the arm/hand area of primary motor cortex, and the resulting signals will be used to command the motions of the participant's arm and hand via thought. The main components of the proposed system are: intramuscular electrodes with percutaneous leads (Ardiem Medical), an external stimulator (FES Center), a BrainGate2 intracortical array and associated external hardware (Neuroport by Blackrock Microsystems), and a standard computer with a real-time operating system (Matlab xPC Target) as the FES controller. Participants will be strongly motivated to optimize the performance of a fully functional system that drives their own paralyzed arms, and they will be given ample opportunity to practice and learn the interfaces. We will test the control performance for three different command interfaces that have been widely used in similar applications: (1) continuous trajectory control used widely in previous BMI research, (2) movement goal-based control widely used to control robotic arms, and (3) state-based gated ramp control used widely to control artificial prosthetic arms. Participants will perform the same set of standard movements as well as functional activities with each interface. We will compare the effectiveness and robustness of each command approach based on technical and functional performance metrics (accuracy, speed, consistency over time, functional performance, ease of use). We will also evaluate the ability of M1 to generate continuous, goal and state commands, and will characterize changes in neural signal properties (tuning and modulation depth) while using these three interfaces. This project will, for the first time, directly test the feasibility of a human intracortical BMI-controlled FES upper limb system, so our results will guide the specifications of future, fully-implanted BMI systems. Our team has 30+ years of experience in developing and testing upper limb FES systems, including in people with complete arm paralysis. We have been working to develop a human intracortical BMI for the past 7 years, have full regulatory approval, and have established a clinical BrainGate2 site in Cleveland. This project is a natural expansion of our past work by combining the FES and BMI approaches in people with SCI. The technical risks of this project are relatively low, but the potential scientific and rehabilitation returns are very high.