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

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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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Data availability

Raw data and analysis software code are available at https://osf.io/jq5hn/.

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Acknowledgements

The authors thank Dr. Sarah Offutt and Dr. Thaddeus Brink for providing comments and discussion, and Eric Kennedy, Dr. Ahmad Jiman, David Ratze, Dr. Jiajie Jessica Xu, Zuha Yousuf, Alec Socha, Vlad Marcu, Manorama Kadwani, Nicholas Peck-Dimit, and Hannah Parrish for assisting with the data collection. The authors also thank the University of Michigan Unit for Laboratory Animal Medicine for assistance with animal care. This study was supported by a research grant from Medtronic and awards from the National Institutes of Health SPARC program (OT2OD023873, OT2OD024907). The opinions expressed in this article are the authors’ own and do not reflect the view of Medtronic or the National Institutes of Health. Drs. Zirpel and Bittner are employees of Medtronic.

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Authors and Affiliations

  1. Biomedical Engineering Department, University of Michigan, Ann Arbor, MI, USA

    Zhonghua Ouyang, Nikolas Barrera, Zachariah J. Sperry, Elizabeth C. Bottorff & Tim M. Bruns

  2. Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA

    Zhonghua Ouyang, Nikolas Barrera, Zachariah J. Sperry, Elizabeth C. Bottorff & Tim M. Bruns

  3. Pelvic Health & Gastric Therapies, Medtronic Restorative Therapies Group, Minneapolis, MN, USA

    Katie C. Bittner & Lance Zirpel

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  1. Zhonghua Ouyang
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Correspondence to Tim M. Bruns.

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Ouyang, Z., Barrera, N., Sperry, Z.J. et al. Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an anesthetized feline model. Med Biol Eng Comput 60, 1527–1540 (2022). https://doi.org/10.1007/s11517-022-02554-8

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