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bioRxiv · 10.1101/2020.05.02.074484

Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an acute feline model

Ouyang, Z.·Barrera, N.·Sperry, Z. J.·Bottorff, E. C.·Bittner, K. C.·Zirpel, L.·Bruns, T. M.
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Abstract

Overactive bladder patients suffer from a frequent, uncontrollable urge to urinate, which can lead to a poor quality of life. We aim to improve open-loop sacral neuromodulation therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 anesthetized felines. We implemented a Kalman filter-based algorithm to estimate the bladder pressure in real-time using sacral-level DRG neural recordings and initiated sacral root electrical stimulation when the algorithm detected an increase in bladder pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to bladder fills with continuous and no stimulation. Overall, closed-loop stimulation increased bladder capacity by 13.8% over no stimulation (p < 0.001) and reduced stimulation time versus continuous stimulation by 57.7%. High-confidence bladder single units had a reduced sensitivity during stimulation, with lower linear trendline fits and higher pressure thresholds for firing observed during stimulation trials. This study demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control of sacral neuromodulation. An underlying mechanism for sacral neuromodulation may be a reduction in bladder sensory neuron activity during stimulation. Real-time validation during behavioral studies is necessary prior to clinical translation of closed-loop sacral neuromodulation.

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Ouyang, Z., Barrera, N., Sperry, Z. J., Bottorff, E. C., Bittner, K. C., Zirpel, L., Bruns, T. M.. 2020-05-03. Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an acute feline model. https://doi.org/10.1101/2020.05.02.074484

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