Boris Prilutsky - US grants

? DESCRIPTION (provided by applicant): There are currently more than 1.7 million persons living in the United States with an amputation (not including finger amputations), a large fraction of whom are upper extremity amputees (over 500,000) (Ziegler-Graham et al., 2008). Hand, trans-radial or trans-humeral amputations cause dramatic loss of an amputee's ability to perform everyday upper extremity tasks. Currently many prosthetic arm users are dissatisfied with available prostheses as 20-45% amputees do not wear body-powered and electric prostheses and prefer to use non- prehensile prostheses as cosmetic devices (Datta et al., 2004; Biddiss & Chau, 2007a; Biddiss & Chau, 2007). We propose to develop a bold and innovative prosthetic device, which is directly attached to residual bone and muscles and allows simple prosthetic control (Farrell & Prilutsky, 2011). This device combines the ideas of bone anchored prostheses with an innovative method of harnessing residual muscles and tendons in the amputated limb to allow them to actuate and sense the external prosthesis with multiple degrees of freedom. This device operates by transmitting force developed by residual muscles via alloplastic tendons passing through the skin and bone integrated implant to the external prosthesis. The central element of the device is the implant with tendon tubes, which allow for frictionless transmission of muscle force and maintenance of skin integrity preventing skin stretch and infiltration of bacteria. The project is a proof-of-concept study with the general goal to develop a prosthetic device that is directly attached to the residual limb and controlled and sensed by the residual muscles. In Specific Aim 1, we plan to develop and refine an implant design for a muscle actuated prosthesis in a rat model. We will implant a group of rats with bone anchored prosthetic foot which is actuated by one ankle extensor and one ankle flexor through connectors sealed inside the residuum. At least two methods of muscle attachments to the artificial foot will be tested: (1) an accordion-like attachment and (2) an elastic tube attachment. In Specific Aim 2, we will evaluate the limits of neuromuscular plasticity that are required to control prosthetic devices by residual muscles. To test the extent to which neuromuscular plasticity can modify activation patterns of the residual muscles after prosthetic device implantation, the residual muscles will be implanted with EMG electrodes and sonomicrometry crystals to measure muscle activity and fascicle length changes in two groups of rats. One group of rats will have the residual muscles to perform their natural functions, i.e. flex or extend the ankle. The function of the residual muscles of the second group will be reversed (similar to tendon transfer) so that the flexor will have an extension action at the joint and the extensor, a flexion action. These studies will provide important information about the design features of the proposed prosthetic device and the plasticity of the neuromuscular system and offer solutions to enhance the device functionality and durability.

Globally nearly 7 million people suffer from consequences of spinal cord injury. Many years of research using animal models lead to the development of current spinal cord injury (SCI) rehabilitation methods, including the epidural spinal cord (ES) stimulation. ES stimulation has been shown to evoke rhythmic locomotor activity in rats, cats and humans, including humans with clinically complete SCI. However, the evoked rhythmic motor patterns do not permit full weight support and often demonstrate non-physiological co-activation of antagonists, atypical locomotor kinematics and muscle synergies, i.e. groups of muscles activated together and producing basic activity patterns that reflect the modular organization of the locomotor control system. Further progress of the promising ES therapies requires a thorough understanding of the mechanisms underlying generation of distinct kinematic and muscle synergies during walking activated by ES of the spinal cord. The overall goal of this project is to determine the contribution of motion-dependent afferent pathways, selected ascending and descending pathways in the spinocerebellar loop, and the central pattern generator (CPG) circuitry to the generation of the distinct kinematic and muscle synergies during normal walking and ES-activated walking in cats with intact and partially transected spinal cord. This goal will be accomplished in experimental and neuromechanical computational studies performed in close collaboration among 4 research groups (Georgia Institute of Technology; Karolinska Institute, Sweden; Drexel University and Pavlov Institute of Physiology, Russia). In Aim 1 we will determine kinematic and muscle synergies during forward walking in the decerebrate cat whose locomotion is activated by ES or by commands from the brain (stimulation of the mesencephalic locomotor region, MLR), and compare them with the synergies generated by a neuromechanical model of hindlimb locomotion. In Aim 2 we will determine characteristics of activity patterns of individual spinal interneurons in the lumbosacral enlargement during MLR-evoked and ES-evoked walking in the decerebrate cat and use the neuromechanical computational model to reproduce and explain the recorded patterns and their differences. In Aim 3 we will determine characteristics of activity patterns of neurons in selected ascending and descending pathways in the spinocerebellar loop during MLR- and ES-evoked locomotion and investigate their effects on locomotor kinematic and muscle synergies in a neuromechanical model of hindlimb locomotion. Aim 4 will determine effects of opening the spinocerebellar loop using a reversible dorsal hemisection of the spinal cord (rDHS, produced by cooling the dorsal half of spinal pathways at the low thoracic level) on kinematic and muscle synergies, as well as on characteristics of activity patterns of the same individual spinal interneurons during MLR-evoked and ES-evoked walking. We anticipate that this study will improve our understanding of how ES, sensory and supraspinal inputs, and CPG contribute to kinematic and muscle synergies during locomotion and thus will provide scientific basis for improvement of ES- stimulation therapies.

Sensory feedback from moving legs is critical for functional and dynamically stable locomotion. Although it is clear that motion-related sensory feedback influences inter-leg coordination and selection of gaits (walking, trotting, galloping, etc.), it is not known which sensory modalities (e.g., muscle length- or force-related signals) and sources of feedback (e.g., hip or knee muscles) mediate these locomotor changes. Therefore, this project aims to understand how sensory neurons providing information about the length of hip muscles regulate interlimb coordination and gait selection. This goal will be accomplished by selectively and reversibly stimulating these sensory neurons in an intelligent, closed-loop, and well-controlled manner. This project will lead to the development of new neural implant tools and associated computational algorithms for an in-vivo manipulation of motion-related sensory signals in a large animal model, the cat. The new findings of this project and the developed methods will substantially enhance our understanding of the mechanisms of sensory locomotor control and contribute to developing novel therapeutic interventions. The proposed multidisciplinary research approaches will also significantly expand the utility and capabilities of the rapidly growing field of optogenetics, enabling transformative research and providing unprecedented new experimental tools for neuroscience. The most noticeable long-term benefits of this work to society will be an improvement in the quality of life for a sizable population of people affected by a wide range of movement deficits, from limb loss to sensory neuropathy. These individuals will benefit from the development of neural interfaces between the nervous and engineering systems controlled by machine learning algorithms. Throughout this project, efforts will be made to recruit and train graduate and undergraduate students from underrepresented groups. Outreach activities will also be organized to share resources, tools, and knowledge with teachers, students, and underrepresented groups. The results of the proposed research and educational activities will be shared with students, scientific communities, and the public through science fairs, publications, workshops, conferences, and the Internet.

The overall goal of this proposal is to characterize the mechanisms of somatosensory control of interlimb coordination and gait selection by spindle afferents of hip muscles in the cat model by developing and utilizing in-vivo an intelligent and closed-loop optoelectronic neural interface system. In particular, in this proposal high-density, efficient, and wirelessly-powered implantable opto-electro (WIOE) neural interface devices will be developed. Each WIOE heterogeneously incorporates an optoelectronic array of 64 transparent microelectrodes and 16 microscale light-emitting-diodes (µLEDs), a system-on-a-chip (SoC), and a power receiver (Rx) coil in an mm3-size package, capable of optogenetic stimulation and electrical recording of neural activities. Wireless telemetry links will be implemented for efficient transcutaneous power and wideband data transmission between an external data-acquisition/control unit and the distributed array of WIOE implants. Multiple WIOE devices will be implanted in selected dorsal root ganglia (DRG) of the cat. Neural activities of DRG neurons, EMG activities of selected muscles of the four limbs, and full-body locomotor kinematics will be recorded, and spindle afferent activities will be manipulated via optogenetic stimulation in selected DRGs during unconstrained cat locomotion. Machine learning (ML) models leveraging the spatiotemporal structures in the signals and mapping afferent activities in DRGs to limb kinematics will be applied for achieving closed-loop control of the optogenetic neuromodulation. The proposed research activities will be conducted by a team of collaborators with complementary research expertise in the areas of bioMEMS, wireless microelectronics, machine learning, artificial intelligence, and behavioral neuroscience. The successful development of the proposed intelligent and closed-loop optoelectronic neural interface will yield a robust building block for a comprehensive set of minimally invasive neural interfaces to study somatosensory control of movement, as well as monitor or treat somatosensory pathological conditions.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.