TY - JOUR T1 - Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an acute feline model JF - bioRxiv DO - 10.1101/2020.05.02.074484 SP - 2020.05.02.074484 AU - Zhonghua Ouyang AU - Nikolas Barrera AU - Zachariah J. Sperry AU - Elizabeth C. Bottorff AU - Katie C. Bittner AU - Lance Zirpel AU - Tim M. Bruns Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/03/2020.05.02.074484.abstract N2 - Overactive bladder patients suffer from a frequent and uncontrollable urge to urinate, which can lead to a poor quality of life. Current sacral neuromodulation therapy uses open-loop electrical stimulation to alleviate symptoms, which limits battery life and can lead to neural habituation. In this study, we aim to improve therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 non-survival, anesthetized felines, in which the sacral-level DRG and spinal roots were exposed bilaterally. A bipolar cuff electrode was placed on a S1 root distal to the DRG for stimulation. Microelectrode arrays were implanted in the same or opposite S1 and/or S2 DRG. We implemented a Kalman filter-based algorithm to estimate the bladder pressure in real-time using DRG neural recordings. The Medtronic Summit Research Development Kit was used to control sacral root 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. Closed-loop stimulation with DRG sensory feedback reduced stimulation time by 57.7% compared to continuous, standard stimulation. Bladder capacity was increased by 13.8% over no stimulation and by 4.3% over continuous stimulation trials (p < 0.001 and = 0.53, respectively). Stimulation reduced the sensitivity of high-confidence bladder single units, with 35.5% lower linear trendline fits and 466.9% 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.Competing Interest StatementThis research was supported in part by Medtronic. Two co-authors are employees of Medtronic. Medtronic did not influence the study outcomes or interpretations to align with any Medtronic-focused interest. ER -