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Zoom: https://umich-health.zoom.us/j/94734899583?pwd=MDNEMjE3QU5xVGgwZzNQajE4UlJQUT09

Overactive bladder (OAB) is a highly prevalent condition which negatively affects the physical and mental health of millions of people worldwide. Sacral neuromodulation (SNM), currently serving ~300,000 patients worldwide, is a promising third-line therapy that provides improved efficacy and minimum adherence issue compared to conventional treatments. While current SNM is delivered in an open-loop fashion, the therapy could have improved clinical efficacy by adopting a closed-loop stimulation paradigm that uses objective physiological feedback. Therefore, this dissertation work focuses on using sacral level dorsal root ganglia neural signals to provide sensory feedback for adaptive SNM a feline model.

This work began with exploring machine learning algorithms and feature selection methods for bladder pressure decoding. A Kalman filter delivered the highest performance based on correlation coefficient between the pressure measurements and algorithm estimation. Additionally, firing rate normalization significantly contributed to lowering the normalized error, and a correlation coefficient-based channel selection method provided the lowest error compared to other channel selection methods.

Following algorithm optimization, this work implemented the optimized algorithm and feature selection method in real-time in anesthetized healthy and simulated OAB feline models. A 0.88 ± 0.16 correlation coefficient fit was achieved by the decoding algorithm across 35 normal and simulated OAB bladder fills in five experiments. Closed-loop neuromodulation was demonstrated using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials.

Finally, closed-loop SNM stimulation with DRG sensory feedback was performed in a series of anesthetized experiments. It increased bladder capacity by 13.8% over no stimulation (p < 0.001). While there was no statistical difference in bladder capacity between closed-loop and continuous stimulation (p = 0.80), closed-loop stimulation reduced stimulation time by 57.7%. Interestingly, bladder single units had a reduced sensitivity during stimulation, suggesting a potential mechanism of SNM.

Overall, this work demonstrated that sacral level DRG are a viable sensory feedback target for adaptive SNM. Validation in awake and chronic experiments is a crucial step prior to clinical translation of this method.