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

Abstract

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.

Can we improve techniques and patients' selection for nerve stimulation suitable for lower urinary tract dysfunctions? ICI‐RS 2023

“…Ouyang et al 16 implemented a Kalman filter-based algorithm to estimate bladder pressure in real-time using sacral-level dorsal root ganglion neural recordings in cats. The system initiated sacral root electrical stimulation when the algorithm detected an increase in the estimated bladder pressure.…”

“…The system initiated sacral root electrical stimulation when the algorithm detected an increase in the estimated bladder pressure. 16 Closed-loop neural stimulation was performed during continuous cystometry, and this was compared to bladder fills with continuous stimulation and no stimulation. Dorsal root ganglion nerves that were found with high confidence to innervate the bladder had reduced sensitivity during stimulation, with lower linear trendline fits and higher-pressure thresholds for nerve firing.…”

“…17 CNS increased bladder capacity by 13.8% over no stimulation with no significant difference in bladder capacity compared to continuous stimulation but with a reduced stimulation time by 57.7% compared to continuous stimulation. 16 Implementation of this method of conditional stimulation would require a nerve recording device in the dorsal root ganglion that can continuously communicate with a sacral root stimulation device. However, electrophysiological function and data from the implant can be degraded with time due to a foreign body response or formation of a multicellular inflammatory encapsulating-scar around the implanted electrodes.…”