Robert Gaunt - US grants

Abstract The loss of normal bladder control that occurs after a spinal cord injury can lead to severe health consequences. In fact, the most common reason for hospitalization in people with spinal cord injuries is urinary tract complications that arise from deficiencies in the current clinical methods to manage bladder function. In addition, social issues surrounding regular bladder care can lead to a decrease in quality of life and surveys indicate that people with spinal cord injury desire improvements in bladder care above many other functions. Several promising approaches to improve bladder function using neurotechnologies have been proposed, however all but a few techniques have failed to reach clinical use. A fundamental limitation with previous approaches is that they have not been able to selectively or simultaneously stimulate the distributed reflex pathways known to contribute to normal function. For example, stimulation of different sensory pathways in the pudendal nerve can elicit both continence and micturition reflexes, however, these reflexes are modulated by sensory activity in the pelvic nerve. Accessing all these pathways in the peripheral nervous systems is extremely challenging. The goal of this proposal is to achieve selective activation of afferent pathways from the bladder, urethra and genitalia by implanting multielectrode arrays into the sacral dorsal root ganglia (DRG). At this interface location, we believe that sensory afferents from both the pudendal and pelvic nerves can be stimulated selectively without activating motor pathways. Using this approach, we plan to independently modulate activity in multiple reflex pathways to the spinal cord and will assess the effect on control of continence and micturition. Specifically, these experiments propose to 1) determine the patterns of afferent recruitment in response to sacral DRG microstimulation, 2) test the effects of single-channel and coordinated multichannel microstimulation of sacral DRG afferents on recruitment of storage and voiding reflexes, and 3) determine the impact of supraspinal reflex pathways on coordinated multichannel microstimulation. Success in these aims will demonstrate that the sacral DRG can be used to enable access to the distributed peripheral pathways of the lower urinary tract. This access could be useful for both fundamental investigations into the neural control of the bladder as well as for development of neuroprosthetic technologies. Ultimately, our long-term goal is to develop a device that leverages knowledge of the spinal control of continence and micturition reflexes to restore functionally normal control of the bladder to people living with injured spinal cords.

Abstract Visceral organs present unique challenges to studying functional physiology and neural control. Visceral organs are often surrounded by a nerve plexus that provides distributed innervation along the organ surface and contain autonomic ganglia that can modulate function locally. Given this complexity, creating functional maps of visceral organ innervation is challenging. Another challenge is measuring organ state itself. This is significantly exacerbated by the fact that many of these organs are soft, elastic, and undergo large volume changes. In this proposal, we will develop soft silicone electrode nets compatible with these unique challenges and that can envelop visceral organs and deploy high-resolution electrodes to arbitrary positions on the organ surface. This approach is based on a 3D printed silicone electrode technology. These electrode nets will be augmented with strain gauge sensors and electrical impedance tomography electrodes to monitor physiological organ state. Ultimately, this new class of devices will 1) be intrinsically soft and elastic to allow conformation with visceral organs that undergo large volume changes, 2) integrate organ state sensors based on strain gauges and electrical impedance tomography, 3) prevent delamination issues typically associated with other thin film electrode manufacturing processes, and 4) allow rapid customization to cost-effectively transition to any organ system in animals or humans. This technology is based on materials that have a history of use in biomedical implants and are therefore potentially suitable for conducting neural mapping and electrophysiological studies of human organs in vivo. We will evaluate device performance using the bladder and urethra as a model due to the challenging interface requirements (e.g. large volume changes) and potential clinical relevance. Overactive bladder and urinary incontinence affects millions of people worldwide, is associated with costs upwards of $60 billion each year in the United States, and leads to significant decreases in quality of life. Electrode nets will be tested in acute cat experiments where we will determine the electrode-tissue mechanical stability, evaluate embedded sensor performance, and develop functional neural maps of the surface of the bladder and urethra. We will also validate device performance in a series of chronic animal experiments where device performance will be monitored for up to four months post-implant. An important feature of this enabling technology and associated manufacturing process is that these devices will be able to be quickly and cost-effectively redesigned to study other visceral organ systems including the stomach, intestines, and colon across a range of animal models as well as humans.