Objective. Neuromodulation is a standard therapy for bladder symptoms such as overactive bladder. Previous studies have demonstrated that non-continuous stimulation (NCS) can increase bladder capacity and that bladder pressure can be estimated from dorsal root ganglia (DRG) neural activity in anesthetized animal models. Our goal is to determine if NCS elicits similar bladder capacity effects as continuous stimulation (CS) and if bladder pressure can be estimated from DRG signals in an awake, unrestrained animal model.Approach. We performed aseptic, chronic implant surgeries with seven adult, male felines. Three animals were used to establish procedures, three for experimental testing, and one did not yield data. Bipolar stimulating electrodes were placed on the pudendal nerve and sacral nerve on the same side. Microelectrode arrays were inserted in two ipsilateral sacral DRG. Two single-lumen catheters were implanted in the bladder dome for recording bladder pressure and infusing saline. Fixed-sequence, repeated bladder fills were performed in four awake felines to evaluate the bladder capacity during no-stimulation (NS), NCS, and CS at either the pudendal or sacral nerve. NCS was performed based on increases in bladder pressure estimated from DRG recordings or when 50% of the average NS bladder capacity was reached.Main results. We observed similar bladder capacity increases for NCS (122± 31% of NS control) as for CS (121± 33%) in the four animals. NCS paradigms reduced stimulation time by 46% on average. Median correlation coefficients of 0.46 and 0.64 (maximum 0.93) between the predicted and measured bladder pressure were obtained for awake trials with DRG bladder units in two animals.Significance. This study demonstrated the feasibility of using NCS to increase bladder capacity in awake, unrestrained felines and for decoding bladder pressure from DRG recordings. Further studies are needed to optimize NCS timing for clinical translation.

Objective. Brain-machine interfaces (BMIs) have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user's own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. Approach. We delivered a nerve block to the median, radial, and ulnar nerves just proximal to the elbow to simulate finger paralysis, then used a closed-loop BMI to predict finger movements the monkey was attempting to make in two tasks. The BCFES task was one-dimensional in which all fingers moved together, and we used the BMI's predictions to control FES of the monkey's finger muscles. The virtual two-finger task was two-dimensional in which the index finger moved simultaneously and independently from the middle, ring, and small fingers, and we used the BMI's predictions to control movements of virtual fingers, with no FES. Main results. In the BCFES task, the monkey improved his success rate to 83% (1.5 s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5 s median acquisition time, equal to the trial timeout) when attempting to use his temporarily paralyzed hand. In one monkey performing the virtual two-finger task with no FES, we found BMI performance (task success rate and completion time) could be completely recovered following temporary paralysis by executing recalibrated feedback-intention training one time. Significance. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting factor in a BCFES neuroprosthesis.

ABSTRACT Introduction and Hypothesis Human menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that tibial nerve stimulation (TNS) or electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that TNS would protect against harmful reproductive and systemic changes associated with menopause. Methods We examined the effects of twice weekly TNS (0.2 ms pulse width, 20 Hz, 2x motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood flow. Rats were split into three groups (n = 10 per group): 1) intact control (no stimulation), 2) OVX control (no stimulation), and 3) OVX stimulation (treatment group). Results TNS did not affect serum estradiol levels, body weight, or blood glucose. TNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control. Conclusion TNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of TNS on menopause-associated symptoms under different experimental conditions are warranted. Summary Percutaneous tibial nerve stimulation increases vaginal blood perfusion, areal bone mineral density, and femur yield load in an ovariectomized rat model of menopause.

ABSTRACT Brain-machine interfaces have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user’s own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. In a one-dimensional, continuous, finger-related target acquisition task, the monkey improved his success rate to 83% (1.5s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5s median acquisition, equivalent to chance) when attempting to use his temporarily paralyzed hand. With two monkeys under general anesthesia, we found FES alone could control the monkeys’ fingers to rapidly reach targets in a median 1.1s but caused oscillation about the target. Finally, when attempting to perform a virtual two-finger continuous target acquisition task in brain-control mode following temporary hand paralysis, we found performance could be completely recovered by executing recalibrated feedback-intention training one time following temporary paralysis. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting performance factor in a BCFES neuroprosthesis.

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes , and Actinobacteria , which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.

Human menopause transition and post‐menopausal syndrome, driven by reduced ovarian activity which reduces estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, osteoporosis, and metabolic disease. Current treatments (both hormonal and non‐hormonal) are limited in efficacy and may have adverse consequences, so investigation for additional treatment options are necessary. Previous studies have demonstrated that tibial nerve stimulation or electro‐acupuncture are minimally invasive treatments that increase vaginal blood flow and serum estrogen in the rat model. In this study we examined the effects of biweekly tibial nerve stimulation (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine‐xylazine anesthesia in female ovariectomized (OVX) Sprague Dawley rats on various measurements that can change in association with menopause (serum estradiol, resting blood glucose, vaginal blood perfusion, uterine weight/histology, and bone density) either at weekly time‐points or during a terminal necropsy. Rats were split into three groups (n = 10 per group): 1) intact + no stimulation, 2) OVX + no stimulation, and 3) OVX + stimulation. Although preliminary data has not shown significant differences between treatment groups, data collection is ongoing and trends are expected after weeks of stimulation. The results of this study will examine the effects of tibial nerve stimulation on various menopause associated symptoms, and help guide recommendations for future studies and treatments.

Objectives: To compare the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and α-chloralose) on anesthetic and urodynamic parameters in felines. Materials and Methods: Adult male cats (n=5) were sedated at least three times per agent with dexmedetomidine (reversed with atipamezole), alfaxalone, and propofol on separate days, and anesthetized one time with isoflurane, then transitioned to α-chloralose during a terminal procedure. At least two cystometrograms (CMGs) were conducted in each sedated session. Urodynamic parameters (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic parameters (change in heart rate [ΔHR], average heart rate [HR], reflexes, induction/recovery times) were evaluated. Results: Δpressure was greatest with propofol (117 ± 10 cm H20), bladder capacity was highest with α-chloralose (60 ± 9 ml), non-voiding contractions (NVCs) were greatest with α-chloralose (0.03 ± 0.01 NVCs/s). Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the CMGs respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine (HR 117 ± 6; ΔHR 19 ± 21 bpm), compared to propofol (HR 174 ± 6 bpm; ΔHR 85 ± 22 bpm) and alfaxalone (HR 211 ± 6 bpm; ΔHR 77 ± 21 bpm). Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. Conclusion: These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choice.