RESEARCH

Completed Projects

Active MEMS Neural Clamps

Key Personnel: R. Jung, PhD (PI); ANS/Bioengineering
S. Phillips, PhD (Electrical Engineering)
J.D. Sweeney, PhD (Bioengineering)

Sponsor: National Institutes of Health, 4/1/05-3/31/08, $403,756

In the past decade, significant technological and scientific advances have led to the development of neuroprosthetic devices for motor control. An important aspect in the further advancement of the control systems for such devices will be the ability to obtain stable spatiotemporally distributed recording of neural activity chronically. Similarly, neural interfaces that can provide spatiotemporally distributed stimulation of neural tissue are required. In this project, we are focusing on the development of a novel approach of recording distributed neural activity from the peripheral nervous system, in particular the mammalian spinal roots. The goal is to model, design, fabricate, test and characterize Microelectromechanical System (MEMS) based neural electrodes that actively clamp onto the spinal roots. This clamping mechanism will provide a reversible secure attachment mechanism to ensure reliable recording of the neural signals. The clamping will be driven by the body temperature at site of the implant. The clamping can be temporarily reversed for repositioning during the implant procedure by local perfusion of cooled saline solutions. The fabrication will use silicon wafer batch processing techniques that are compatible with integrated circuit manufacturing in order to enable future development of on-chip electronics for filtering, amplification and signal processing. The silicon wafer fabrication also enables future development of low-cost devices. With batch processing, we can vary the electrode and device characteristics on a single wafer to optimize performance. Several electrode configurations on the same device will be evaluated initially using amphibian nerve, then with fixed rodent nerve, and ultimately in real-time by recording autonomous respiratory activity from rat cervical spinal roots and the phrenic nerve. Ability to place the electrodes on multiple lumbosacral spinal roots will be evaluated. These results will guide the redesign of the electrodes. The novel design allows capability for repositioning of multiple spatially distributed implantable electrodes. Such electrodes will advance our capabilities of scientific investigation of neural function in awake subjects and in the development of advanced neuroprosthetic products for rehabilitation.


A Rodent Model for Locomotor Training with FNS

Key Personnel: R. Jung, PhD (PI)
J.J. Abbas, PhD (ANS/Bioengineering)

Sponsor: National Institutes of Health (NCMRR_NICHD; R01HD40335), 1/17/02- 6/30/06, $775,418

The long-term goal of this work is to develop strategies for using functional neuromuscular stimulation (FNS) of paralyzed muscles to enhance the recovery of individuals with incomplete spinal cord injury. The proposed work is motivated by three important developments. First, recent basic science and clinical studies have demonstrated that the degree of functional recovery of the injured spinal cord depends on the activity patterns of neural inputs to the spinal cord.

Second, recent advances have produced adaptive controllers for FNS systems that provide a means of automatically adjusting stimulation parameters to reliably achieve specified rhythmic movements.

Third, rodent models of spinal cord injury (complete and incomplete lesions) are extensively being used at the molecular, cellular, and systems level to investigate the effects of traumatic injury and to assess the results of therapeutic intervention. A combination therapy that utilizes locomotor training with FNS and pharmacological intervention is likely to be the most effective in enhancing the reorganization (plasticity) of the spinal circuitry that is spared after spinal trauma. A rodent model for FNS-assisted locomotion would facilitate quantitative evaluation of therapeutic regimens that include FNS and would provide the ability to characterize effects of FNS-assisted locomotion on the neuroanatomy and neurophysiology of the injured spinal cord.

This biomedical engineering research grant proposal will develop a rodent model of locomotor training that utilizes treadmill walking and functional neuromuscular stimulation (FNS) with fixed-pattern and adaptive controllers. Kinematic and electromyogram (EMG) patterns of intact animals will be examined and then used to develop stimulation patterns for FNS-assisted movement. A series of tasks will be performed using FNS stimulation of hindlimb muscles in spinalized rats. These tasks will progress in difficulty from controlling suspended hindlimb movements to controlling hindlimb movements during treadmill locomotion in spinalized rats with partial weight support. Two different FNS control strategies will be used for each movement: a fixed-pattern, or open-loop, stimulation pattern and an adaptive stimulation control system. The adaptive stimulation control system will build upon our previous work and is expected to provide movement patterns that are more accurate and more repeatable.

Successful completion of the proposed project will result in a novel animal model for FNS-assisted locomotor training and provide quantitative methods for evaluating locomotor behavior. In future studies, we plan to use a rodent model of incomplete spinal cord injury with FNS-assisted locomotion to test the hypothesis that FNS-assisted locomotor training enhances motor recovery after incomplete spinal cord injury. We anticipate that the improved performance provided by the adaptive control system may enhance the therapeutic effects of the technique. This locomotor training could also be combined with pharmacological intervention, tissue transplant, and neural repair therapies to determine if locomotor training can enhance the effectiveness of these therapies.


Adaptive Electrical Stimulation for Locomotor Retraining

Key Personnel: James J. Abbas, PhD (PI); ANS/Bioengineering
Ranu Jung, PhD (ANS/Bioengineering)
Richard Herman, MD (Banner Good Samaritan Medical Center)

Sponsor: NIH-National Center for Medical Rehabilitation Research
7/1/05-6/31/08, $868,573
primary contract to ASU with subcontract to Banner Good Samaritan

Recent studies have indicated that functional recovery of locomotor function after spinal cord injury may be enhanced by performing repetitive stepping movements on a treadmill with a harness for partial body weight support with passive assistance provided by therapists. The putative mechanism that underlies this recovery is activity-dependent plasticity of neural circuits both in the spinal cord and in supraspinal centers. Although results in some subjects have been encouraging, in general, the functional gains that have been demonstrated from locomotor therapy are moderate and there is a high variability across subjects. We believe that the ‘standard’ form of this therapy (treadmill/harness with passive assistance from therapists) is soundly based on well-established principles of motor learning, but the manner in which the therapy is delivered does not enable maximization of the therapeutic effect.

We propose that locomotor therapy may be enhanced by: 1) producing sensorimotor patterns that are more ‘physiological’ - i.e. that include appropriately timed muscle contractions and are therefore more similar to sensorimotor patterns in the intact state and 2) generating movement patterns in a more repeatable manner. Our approach utilizes adaptive control of electrical stimulation to activate muscles in order to generate repeatable movements on the treadmill. We believe that the combination of appropriately-timed contractions and repeatable movement patterns will result in an improved form of locomotor therapy. Furthermore, the adaptive nature of the control system may be used to encourage gradual increases in voluntary input, therefore providing a mechanism for weaning the individual from FES-assistance during locomotion.

The long-term goal of this work is to develop a system that will provide a more effective and efficient form of locomotor retraining therapy. In this work, we will develop a technique that uses adaptive control of electrically-stimulated muscles to produce repeatable stepping movements with coordinated sensorimotor patterns of activity. The system will use transcutaneous neuromuscular stimulation to assist in movement generation while walking on the treadmill with partial body weight support provided by a harness. Adaptive control techniques will be used to automatically determine an appropriate set of stimulation parameters for a given individual and to automatically adjust the stimulation parameters to account for fatigue and/or motor retraining effects. The goals of the proposed project are to develop the adaptive system and to evaluate its ability to generate specified movement patterns. We will implement the adaptive system and experimentally demonstrate that it is capable of reliably producing stepping movements by individuals with spinal cord injury on a treadmill with partial body weight support. In future work (beyond the scope of this proposal), we will compare the efficacy of adaptive FES-assisted locomotor therapy with other forms of locomotor therapy.


CRCNS - Modeling Neuromusculoskeletal Alterations after Spinal Cord Injury

Key Personnel: R. Jung, PhD (PI); ANS/Bioengineering
J.J. Abbas, PhD (ANS/Bioengineering)
A. Iarkov, PhD (ANS)
T. Hamm, PhD (Barrows Neurological Institute)
V. Booth (University of Michigan)

Sponsor: National Institutes of Health (NIBIB; NS054282-01)
8/15/05- 7/31/09, $1,314,799

The interaction between neural and musculoskeletal systems enables us to perform a variety of motor tasks, such as locomotion, in a robust and adaptable manner. Damage to one system component, e.g. traumatic spinal cord injury, can lead to long-term secondary changes in other system components due to their close interactions and their inherent plasticity. In some instances, these secondary changes may be maladaptive, and therefore result in further reduction in functional capacity; in other instances, the changes may be favorable, and therefore result in recovery of function. In this work, a series of experimental studies in uninjured and incomplete spinal cord inured (iSCI) rodents will drive the development of a detailed mathematical model of the biomechanics and neural control of the rodent hindlimb. This model will be used to investigate the role of complex interactions amongst impaired central drive, spinal reflexes and musculoskeletal changes after iSCI in the design of appropriate therapy.

Specifically, a chronic rodent thoracic contusion spinal cord injury preparation will be used to investigate the intrinsic intracellular electrophysiology of spinal motoneurons and their afferent control and the intrinsic musculoskeletal properties present after iSCI. The experimental data will guide development of a computational model with neural and dynamic musculoskeletal components. Hodgkin-Huxley type neuron representations will be used to model the local spinal neural circuits that include motoneurons, interneurons and afferents involved in specific spinal reflexes. The musculoskeletal model will incorporate experimentally-determined geometrical musculotendon paths, inertial properties, muscle fiber properties, and 3D laser scanned bony surface geometries. The comprehensive model will consequently be used to test hypotheses regarding the roles of specific ionic currents, altered central drive, altered musculoskeletal properties and altered sensory reflex gain on control of limb movement after iSCI. Successful completion of the work will provide novel information that could help guide the development of efficient treatment techniques and appropriate rehabilitative therapies for enhancing functional locomotor recovery and quality of life for some of the 200,000 people currently living with spinal cord injury related mobility, employability and secondary health related limitations in the United States of America.


Catalyst- Center of Excellence for Adaptive Neuro-Biomechatronic Systems (CEANS)

Key Personnel: R. Jung, PhD (PI); ANS/Bioengineering
J.J. Abbas, PhD (ANS/Bioengineering)
Sharon Crook, PhD (Math/SOLS)
Carlos- Chavez-Castillo, PhD (Math)
Anthony Garcia, PhD (Bioengineering)
Lokesh Joshi, PhD( Biodesign/Bioengineering)
Yung Kuang, PhD (Math)
Anshuman Razdan, PhD (PRISM)
Stephen Phillips, PhD (Electrical Engineering)
Marco Santello, PhD (Kinesiology)
Joseph Wang, PhD (Biodesign/Chemistry)

Sponsor: National Science Foundation (Science of Learning Centers Program)
8/15/2005-7/31/2006 , $133,118

When using a tool or a device, a person must learn to interact with it appropriately in order to accomplish the task at hand. We learn to swing a hammer in a manner that strikes the nail accurately; we learn to press the brake with an appropriate level of force to decelerate the car smoothly; and we learn to move a computer mouse in order to proficiently utilize software. As technology becomes increasingly complex in its operations, its functionality, and its degree of interaction with the user, there is a growing need to embed adaptability and intelligence into the device itself. In this situation, the device and the user simultaneously learn in an attempt to optimize their interactions. The degree of success in this sensorimotor learning process depends strongly on the interaction between the person and the engineered system.

The focus of the Center of Excellence in Adaptive and Neuro-Biomechatronic Systems (CEANS) will be to understand and to optimize the learning that occurs as humans interact with adaptive technology. The Center will focus its efforts on addressing a few broad questions: What are the biological processes that occur as a person learns to interact with a device? How do the properties of the device affect the learning process? How can we design engineering devices to maximize the effectiveness of the learning process?

CEANS will use advanced prosthetic systems as a research platform to address these questions regarding the nature of the sensorimotor learning process and to develop strategies for the design of adaptive systems to achieve specific learning outcomes.

After a traumatic injury such as limb loss or spinal cord injury, technology can assist in tasks such as stepping, reaching or grasping. Several intelligent robotic devices and electrical stimulation systems with adaptive capabilities that are either on the market or on the horizon require that the person learn to use the device as the device adapts to meet the needs of the person. CEANS will use these types of co-adaptive prosthetic systems to investigate the molecular, cellular and systems-level dynamics of sensorimotor learning.

Our goal for this Catalyst project is to lay the foundation for a Science of Learning Center that addresses key issues regarding learning in the integration of adaptive biological systems with adaptive engineered systems. In the planning period, we will develop a proposal for a Center that integrates interdisciplinary research and development with educational and outreach programs.

Our research agenda will be at the intersection of molecular biology, neuroscience, mathematics, bioengineering, and rehabilitation. CEANS will draw upon a wide range of expertise to discover the principles that govern activity-dependent learning in living systems, to develop novel approaches to sense dynamic changes in adaptive living systems, and to deliver new adaptive technology for sensorimotor learning. The scope of activities will include experimental biological investigation, design and development of new technology to maximize learning outcomes, the evaluation of the effects of the technology on biological learning processes, and the transfer of these techniques to biomedical industry and clinical practice.


Promoting Plasticity after Spinal Cord Injury using Neuromuscular Stimulation

Key Personnel: Ranu Jung, PhD (PI); ANS/Bioengineering
James J. Abbas, PhD (ANS/Bioengineering)
Seung-Jae Kim, PhD (ANS)
Alex Iarkov, Phd (ANS)

Sponsor: Science Foundation Arizona (Competitive Advantage Award)
07/1/08-06/30/09, $274,000

Approximately 250,000 individuals with spinal cord injury (SCI)
currently live in the US and approximately 11,000 people acquire new spinal injuries each year. The injuries leave people completely or partially paralyzed. There is a strong international effort for finding a cure for paralysis and many approaches trying to ameliorate the effects of spinal cord injury are being explored. In the proposed work, the neuroprosthetic technology (adaptive algorithms and neural interfaces using functional neuromuscular stimulation) will be used to provide sensorimotor rehabilitation therapy in a rodent model of spinal cord injury. Successful outcome will identify mechanisms that could be specifically targeted by the interventional therapies to promote sensorimotor recovery after incomplete spinal cord injury. The award is specifically directed towards collection of preliminary data.

7T/30 Bruker Biospec Magnetic Resonance Imaging/Spectroscopy System
(Previously PharmaScan 70/16 In-Vivo Spectroscopy/Imaging System)

Key Personnel: Ranu Jung, PhD (P.I. Arizona Sate University)
Faculty from Arizona State University
Faculty from Good Samaritan Medical Center (Eric Reiman, MD)
Faculty from Barrows Neurological Institute (Mark Preul, MD, Adrienne Scheck, MD, Jim Pipe, PhD)


Sponsor: NIH-National Center for Research Resources

6/1/05-5/31/06, $1,309,550

With recent genetic and molecular advances, small animal (rat/mice) models of human disease have become increasingly important resources for the investigation of the underlying mechanisms of disease. Many traditional investigational approaches require sacrificing the animals for ex vivo tissue and molecular analysis. This prevents the researchers from observing in vivo the natural or perturbed evolution of the processes under study. Additionally, small animal models are becoming increasingly important test beds to investigate the ability of novel implantable miniaturized devices and biomaterials to repair, regenerate or replace the living system. Imaging on the scale of small animals offers an opportunity to noninvasively repeat investigations of biological processes in vivo in the same animal and efficiently test treatments for disease.

One approach for bioimaging is to use nuclear magnetic resonance. The ability to perform in vivo imaging and spectroscopy in small animals or large tissue samples is absent at Arizona State University. The gap is further enhanced because of a lack of such a capability in the entire Metropolitan Phoenix Valley area that is home to several excellent clinical and research medical facilities The distance to the closest facility (120 miles) is not conducive to conducting longitudinal chronic studies on large numbers of small animals to support the needs of research in the Phoenix Valley. We were recently awarded funding for a multipurpose research scanner for high resolution, fast speed, Nuclear Magnetic Resonance 2D and 3D image reconstruction and in vivo spectroscopy. Several investigators will significantly benefit from utilizing this system in their research. The applications will range from assessing effects of chemotherapy for tumors, to developing, testing, and implementing noninvasive, brain-imaging indicators of Alzheimer’s Disease (AD) in double transgenic mice containing AD genes, to assessment of CNS neuroplasticity after spinal cord injury or stroke.


Neuromorphic Control System for Powered Limb Splints

Key Personnel: R. Jung, PhD (PI, AdveNSys, LLC)
J.J. Abbas, PhD (PI on ASU subcontract); ANS/Bioengineering

Sponsor: U.S. Army

AdveNSys will develop a suite of products to provide new orthotic and prosthetic options for people with lower limb dysfunction or lower limb amputation. We will enhance our biologically-inspired adaptive neuromorphic control systems technology and integrate it with biomorphic compliant actuators, advanced sensor systems, and lightweight orthotic/prosthetic components to produce a suite of products to provide locomotion assistance. These systems will be used for acute-care in combat settings to provide functional bipedal mobility to injured soldiers. In addition, the systems will be used in post-acute and chronic care situations to enable injured individuals to more fully participate in a wide range of activities in military and civilian settings.

AdveNSys will partner with clinical, industrial and academic research institutions to design, develop and evaluate this next-generation product suite that promises to revolutionize technology to overcome lower limb dysfunction both in military and civilian settings. The Phase II efforts will help mature the AdveNSys technology and deliver critical engineering models that will serve as the basis for development of production prototypes for mass production. It is a critical step in AdveNSys vision to Advancing Everyday Mobility for the 7.4 million people who currently use assistive technology devices for mobility impairments.

 

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