Patrick E. Crago - US grants

The objectives of this project are to study the properties and mechanisms of regulation of muscle contractions in the hand. The results will be used to evaluate and extend theories of stretch reflex function. Mechanical and electromyographic responses to controlled changes in joint angle will be measured in normal human subjects. The components of the total response are due to (i) passive viscoelastic properties at the joint, (ii) dynamic mechanical properties of muscle, and (iii) reflexes from muscle stretch receptors, and each will be assessed individually. The dependence of each of the response components on the magnitude and time course of the test disturbance and on the torque and angle prior to the disturbance will be studied. This will allow a comprehensive evaluation of the regulatory action of stretch reflexes. In particular, the hypothesis that muscle stiffness is regulated will be tested. In addition, the mechanism of reflex action will be assessed by measuring the reflex compensation for an internal disturbance. The gains of the length and force feedback pathways from muscle spindles and tendon organs, respectively, will be calculated from reflex responses obtained before and after the muscle gain is altered by fatiguing exercise. Thus, the relative contributions of muscle spindles and tendon organs to the total response can be quantitated. The results of this project will provide a comprehensive data base for the clinical evaluation of patients with movement disorders (eg stroke, cerebral palsy, Parkinson's disease). In addition, the techniques developed will be directly applicable to studies directed at understanding the mechanisms of disorders of the stretch reflex. The results can be directly applied to the design of feedback control systems in neuroprostheses for the restoration of lost motor function.

hand; neuromuscular stimulator; paralysis; spinal cord injury; biomedical equipment development; bioengineering /biomedical engineering; nervous system prosthesis; fingers; model design /development; electrodes; biomechanics; mathematical model; wrist; elbow; arthrodesis; sensory feedback; human subject;

The objective of this contract is to study closed-loop control of hand grasp by functional neuromuscular stimulation (FNS) is an environment outside the laboratory. The Contractor shall also investigate the feasibility of integrating wrist control, pronation and supination of the forearm, and elbow control into FNS hand grasp systems. These studies will be conducted, in part, in human subjects who have paralyzed upper extremities as a result of upper motor neuron lesions.

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): [unreadable] The objective of this interdisciplinary training program is to train PhDs in the basic engineering and science aspects of assistive technology and in the clinical application of this technology in rehabilitation. Interdisciplinary training is required for engineers to successfully design devices and techniques that meet real clinical needs. PhD training will cover the full range of areas that are required to successfully integrate technology into rehabilitation practice, including both didactic and one-on-one mentorship in the areas of i) basic engineering and medical sciences, ii) biomedical engineering, iii) movement and sensory synthesis, iv) implementation of neuroprostheses, and v) clinical rehabilitation. Thus, the trainees will learn principles that will allow them to extend their research capabilities beyond their focused dissertation research. The development, testing and clinical deployment of neural prostheses provides a particularly relevant vehicle for integrated training and will serve as the primary research training model. We also include training in related biomechanical and neural aspects of motor control. For neuroprostheses, perhaps no alternative short of actual regeneration of neural tissue can restore the equivalent level of function. Electrical interfaces to the nervous system may be used to excite, inhibit, or record from either motor or sensory nerves. It is conceptually possible, therefore, to obtain artificial control with electrical stimulation over virtually all structures that rely upon neural communication. This encompasses most of the critical motor and sensory pathways involved in paralysis of the central nervous system as a result of injury or disease such as spinal cord injury, stroke, and Parkinson's disease. This technology can thus restore function to individuals who have sustained such damage, and implantable systems of this type have been approved for commercial deployment. The participating faculty are experts in the fields of engineering and rehabilitation, including the design and deployment of neuroprostheses and neuromuscular modeling, assessment, analysis, and synthesis. The facilities of the training mentors at the participating institutions are accessible to the trainees, and include basic science and engineering laboratories, neuroprosthesis development laboratories, and clinical outpatient laboratories. [unreadable] [unreadable]

How does the nervous system control muscles whose function changes with their mechanical context? To answer this question, Dr. Chiel is studying muscles in an animal, the marine mollusk Aplysia californica, whose biomechanics and neural control are both tractable to experimental
analysis. To test the hypothesis that the function of the muscles I1/ I3 during feeding are dependent on their mechanical context, he will study the changing position of I1/ I3 relative to other muscles in the feeding apparatus in intact, feeding animals using MRI, as well as constructing a detailed kinematic model. Using neurophysiological techniques, he will also
determine whether the nervous system of the animal exploits the context-dependent properties of the I1/I3 muscles to generate different movements during biting as opposed to swallowing.
The proposed research is likely to suggest principles that will clarify the control of context-dependent muscles in higher vertebrates as well as in invertebrates. These studies will lead to the development of novel MRI imaging techniques that may be applied to many other freely
moving biological structures. Finally, these studies suggest a richer view of motor control, in which motor patterns are not purely driven by activity of the nervous system, but are actively constructed from the dynamics of the body as well as the dynamics of the nervous system.

0125703
Wagner

This award is to Case Western Reserve University (Lead Institution) to support the activity described below for 36 months. The proposal was submitted in response to the Partnerships for Innovation Program Solicitation (NSF 0179).

Partners
The partners in the proposed effort include: Case Western Reserve University (Lead Institution), Cleveland Clinic Foundation, Inc., KAL Equity Capital Fund, Metro Health Medical Center, Nortech-Northeast Ohio Technology Coalition, Ohio Innovation Fund, Seven Roien Funds, University Hospitals of Cleveland, Edison Biotechnology, Inc., CID Equity Partners, Enterprise Development Inc.

Proposed Activities
The award has the following activities: (1) internships for local high school students to work at Case Western Reserve University and the Cleveland Bio Technology Park, (2) academic degree programs for undergraduate students to take one semester of bioengineering and management and internships for post graduates as part of the master's degree, (3) research activities in bioengineering or biomedical design where students design a product plus a business plan for its commercialization, (4) technology transfer with the use of a new incubator activity.

Proposed Innovation
The goal of the effort is to change the culture in Northeast Ohio to promote vibrant entrepreneurship by attracting young people to biotechnology, creating new biomedical undergraduate and graduate entrepreneur track degree programs that combine engineering and management studies, funding for biology-related entrepreneurs for early evaluation of product concepts and commercialization, and mentoring for entrepreneurs by successful business partners.

Potential Economic Impact
The award will allow the Northeast Ohio region to apply its considerable academic research and education strengths to entrepreneurial endeavors that will generate economic development. The goal is for the region to become one of the top ten regions for biomedical industry employment by the year 2010.

Potential Societal Impact
Young people will be recruited for careers in biotechnology and be given education in both engineering and management to prepare them to become entrepreneurs to lead the new biotechnology economy that will be one of the top ten in the nation by 2010. The emphasis on recruit and education of under-represented minorities is a major societal benefit.

implant; arm; neuromuscular stimulator; muscle function; spinal cord injury; elbow; performance; nervous system prosthesis; paralysis; sensorimotor system; medical implant science; clinical research; human subject;

This Partnerships for Innovation (PFI) project--a Type III (A:C) partnership between Case Western Reserve University (CWRU), a NSF PFI graduate (0125703), and Lorain County Community College (LCCC), an institution new to the PFI Program (defined as one that has never been a PFI grantee)--seeks to create novel biotechnology innovation in a region facing economic change of major impact by constructing a relationship among a research university, a community college, and technology-based economic development organizations. Students and faculty members from each institution will be integrally involved in prospective and competitive funding for selected Innovation Projects that take ideas from their origins through successive iterations of a disciplined innovation process, including market assessment, design, and development, prototyping, and market readiness. The institutional interactions between CWRU and LCCC will be facilitated by a Relationship Manager, a novel administrative position that ensures inter-institutional alignment, student mentoring within CWRU and LCCC, and a strategic mechanism by which students are assigned to project teams. Each Innovation Project will be under the leadership of an entrepreneur-in-residence provided by TechLift, a technology based development organization. The intellectual merit resides, in part, in the novel links and resulting synergies of faculties, students, and business people with different complementary skill-sets. It links the discovery process of universities to the workforce development missions of community colleges.

The project seeks to align institutional activities with regional economic needs so the latter are more nationally and internationally competitive, especially in a regional economy in the throes of change. It is planned that this pilot partnership will not only be sustained and expanded between Case Western Reserve University (CWRU) and Loraine County Community College (LCCC), but it will also serve as a test-bed for LCCC's relationships to other higher education institutions in the region, although each future innovation partnership will have to be attuned and managed according to its distinct properties.

Partners at the inception of the project are Academic Institutions: Case Western Reserve University (CWRU) (lead institution) and Lorain County Community College; and Private Sector Organizations: Great Lakes Innovation and Development Enterprise (GLIDE), and TechLift.