The overall objective of this functional bladder mapping study is to identify the spinal cord epidural
stimulation (scES) configurations (anode/cathode selection, amplitude, frequency and pulse width) at the
lumbosacral level that can promote neural control of bladder storage (capacity) and voiding efficiency after
spinal cord injury (SCI). This comprehensive functional mapping study in both humans and animals in parallel
involves a novel clinical application of a marketed Medtronic device for bladder dysfunction after SCI. The
mapping (human and animal) and training (human) experiments address several specific objectives of the
SPARC Program initiative per RFA-RM-15-018 including neural circuit maps regarding functional connectivity
(Aim 1), neural plasticity related to stimulation (bladder training experiments – Aim 2), variability (animal-to-
animal and patient-to-patient), and research on what organ functions results from different types of stimulation
(storage vs voiding and identifying any additional effects on bowel and/or sexual function).
The long-term reduction in the cost to the health care system, care givers and society would be
dramatic. SCI results in impairments of locomotor, sensory and autonomic functions, severely affecting overall
health and quality of life. Proper bladder management post-SCI is necessary to decrease the risk of upper
urinary tract disease, a major source of morbidity. Life-long urologic care is required for SCI individuals, yet
most efforts treat symptoms but do not improve intrinsic function. Current therapies for bladder management
after SCI include catheterization, pharmacologic and surgical interventions, functional electrical stimulation
(peripheral), and urethral stents, but all have deleterious effects. We have exciting data from multiple
individuals with severe injuries (AIS A and B) indicating improved bladder function after undergoing a widely
implemented activity-based rehabilitation, locomotor training (LT), which includes stepping using body weight
support on a treadmill with manual facilitation. In addition, we have intriguing preliminary data from several
completely paralyzed individuals receiving scES in combination with task specific training that recovered
standing and voluntary movement and showed improvements in both bladder capacity and voiding efficiency.
Our most recent pilot data also indicate an immediate benefit of scES alone on bladder function. Thus, we
propose to determine the functional gains that can be achieved in the storage and voiding phases of lower
urinary tract function as a result of activation of spinal circuits with scES in humans with SCI and in a clinically-
relevant rodent SCI model. We will test the general hypothesis that bladder capacity and voiding efficiency
increases with scES post-SCI and to an even greater extent with scES bladder training over time.
This proposal involves the collaboration of clinicians and scientists with extensive experience in animal
and human SCI models. Our unique approach will utilize the expertise of a multi-disciplinary team (expertise in
bladder function, neuromodulation, rehabilitation, engineering, and statistics) to 1) determine the optimal
stimulation parameters for storage and voiding in SCI research participants already implanted with the scES
Medtronic device (16-electrode array from L1-S1); 2) quantify the long-term effects of daily bladder training
using optimal stimulation parameters (all the same research participants); 3) measurement of secondary
benefits (bladder medication usage, susceptibility to urinary tract infections, indirect cardiovascular, bowel and
sexual function benefits) of long-term bladder training; and 4) address with a small animal model the impact of
location, lesion severity, chronicity and gender. Our innovative approach and novel application of this
Medtronic Specify 5-6-5 device will allow us to determine specific types of scES needed for bladder function
which will lay the groundwork for expedient translation of this promising technique to larger numbers of
individuals with SCI in the next phase of the SPARC initiative, with additional refinement in parallel using a
large animal SCI model (pig) that is currently under development within the Kentucky Spinal Cord Research
Center.