Objective
Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways.
Approach
Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity.
Main results
LUT single- and multi-unit activity was recorded for 4 to 11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 days, and we tracked individual single-units for up to 23 days continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded.
Significance
This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.
Overactive bladder (OAB) patients suffer from a frequent urge to urinate, which can lead to a poor quality of life. Current neurostimulation therapy uses open-loop electrical stimulation to alleviate symptoms. Continuous stimulation facilitates habituation of neural pathways and consumes battery power. Sensory feedback-based closed-loop stimulation may offer greater clinical benefit by driving bladder relaxation only when bladder contractions are detected, leading to increased bladder capacity. Effective delivery of such sensory feedback, particularly in real-time, is necessary to accomplish this goal. We implemented a Kalman filter-based model to estimate bladder pressure in real-time using unsorted neural recordings from sacral-level dorsal root ganglia, achieving a 0.88 ± 0.16 correlation coefficient fit across thirty-six normal and simulated OAB bladder fills in five experiments. We also demonstrated closed-loop neuromodulation using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials. An offline analysis indicated that unsorted neural signals had a similar stability over time as compared to sorted single units, which would require a higher computational load. We believe this study demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control; however, real-time validation during behavioral studies is necessary prior to clinical translation.
Overall, the GSEA has been shown to provide a variety of information types from ganglia neurons and to have significant potential as a tool for neural mapping and interfacing.
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