Biology subjects

Bruns, T. M.

Publications and source records attributed to Bruns, T. M..

12 recordsLinked to original sources

bioRxiv2024

Non-continuous neuromodulation in awake, unrestrained felines increases bladder capacity

ObjectiveNeuromodulation 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. ApproachWe 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 resultsWe 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. SignificanceThis 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.

bioengineering↗

bioRxiv2023

Multiformity of extracellular microelectrode recordings from Aδ neurons in the dorsal root ganglia: A computational modeling study

Microelectrodes serve as a fundamental tool in electrophysiology research throughout the nervous system, providing a means of exploring neural function with a high resolution of neural firing information. We constructed a hybrid computational model using the finite element method and multi-compartment cable models to explore factors that contribute to extracellular voltage waveforms that are produced by sensory pseudounipolar neurons -- specifically, smaller A-type neurons -- and that are recorded by microelectrodes in dorsal root ganglia. The finite element method model included a dorsal root ganglion, surrounding tissues, and a planar microelectrode array. We built a multi-compartment neuron model with multiple trajectories of the glomerular initial segment found in many A-type sensory neurons. Our model replicated both the somatic intracellular voltage profile of A{delta} low-threshold mechanoreceptor neurons and the unique extracellular voltage waveform shapes that are observed in experimental settings. Results from this model indicated that tortuous glomerular initial segment geometries can introduce distinct multiphasic properties into a neurons recorded waveform. Our model also demonstrated how recording location relative to specific microanatomical components of these neurons, and recording distance from these components, can contribute to additional changes in the multiphasic characteristics and peak-to-peak voltage amplitude of the waveform. This knowledge may provide context for research employing microelectrode recordings of pseudounipolar neurons in sensory ganglia, including functional mapping and closed-loop neuromodulation. Further, our simulations gave insight into the neurophysiology of pseudounipolar neurons by demonstrating how the glomerular initial segment aids in increasing the resistance of the stem axon and mitigating rebounding somatic action potentials.

neuroscience↗

bioRxiv2022

Ultra-flexible and Stretchable Intrafascicular Peripheral Nerve Recording Device with Axon-dimension, Cuff-less Microneedle Electrode Array

Peripheral nerve mapping tools with higher spatial resolution are needed to advance systems neuroscience, and potentially provide a closed-loop biomarker in neuromodulation applications. Two critical challenges of microscale neural interfaces are (i) how to apply them to small peripheral nerves, and (ii) how to minimize chronic reactivity. We developed a flexible microneedle nerve array (MINA), which is the first high-density penetrating electrode array made with axon-sized silicon microneedles embedded in low-modulus thin silicone. We present the design, fabrication, acute recording, and chronic reactivity to an implanted MINA. Distinctive units were identified in the rat peroneal nerve. We also demonstrate a long-term, cuff-free, and suture-free fixation manner using rose bengal as a light-activated adhesive for two timepoints. The tissue response at 1-week included a sham (N=5) and MINA-implanted (N=5) group, and the response at 6-week also included a sham (N=3) and MINA-implanted (N=4) group. These conditions were quantified in the left vagus nerve of rats using histomorphometry. Micro-CT was added to visualize and quantify tissue encapsulation around the implant. MINA demonstrated a reduction in encapsulation thickness over previously quantified interfascicular methods. Future challenges include techniques for precise insertion of the microneedle electrodes and demonstrating long-term recording.

neuroscience↗

bioRxiv2021

Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rats

Introduction and HypothesisHuman 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. MethodsWe 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). ResultsTNS 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. ConclusionTNS 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. SummaryPercutaneous tibial nerve stimulation increases vaginal blood perfusion, areal bone mineral density, and femur yield load in an ovariectomized rat model of menopause.

physiology↗

bioRxiv2021

Sharpened and mechanically robust carbon fiber electrode arrays for neural interfacing

Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers were sharpened using a reproducible blowtorch method that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 {+/-} 33.5 degree tip angle with 146.8 {+/-} 17.7 m exposed carbon. Silicone-embedded carbon fiber arrays were durable with 87.5% of fibers remaining after 50,000 passes. Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat CVN (41.8 Vpp), feline DRG (101.1 Vpp), and rat brain (80.7 Vpp). Recordings from the feline DRG included physiologically-relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recording device. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.

bioengineering↗

bioRxiv2020

High-density Neural Recordings from Feline Sacral Dorsal Root Ganglia with Thin-film Array

Objective: Dorsal root ganglia (DRG) are promising sites for recording sensory activity. Current technologies for DRG recording are stiff and typically do not have sufficient site density for high-fidelity neural data techniques. Approach: In acute experiments, we demonstrate single-unit neural recordings in sacral DRG of anesthetized felines using a 4.5 m-thick, high-density flexible polyimide microelectrode array with 60 sites and 30-40 m site spacing. We delivered arrays into DRG with ultrananocrystalline diamond shuttles designed for high stiffness affording a smaller footprint. We recorded neural activity during sensory activation, including cutaneous brushing and bladder filling, as well as during electrical stimulation of the pudendal nerve and anal sphincter. We used specialized neural signal analysis software to sort densely packed neural signals. Main results: We successfully delivered arrays in five of six experiments and recorded single-unit sensory activity in four experiments. The median neural signal amplitude was 55 V peak-to-peak and the maximum unique units recorded at one array position was 260, with 157 driven by sensory or electrical stimulation. In one experiment, we used the neural analysis software to track eight sorted single units as the array was retracted ~500 m. Significance: This study is the first demonstration of ultrathin, flexible, high-density electronics delivered into DRG, with capabilities for recording and tracking sensory information that are a significant improvement over conventional DRG interfaces.

bioengineering↗

bioRxiv2020

Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array

Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 m in diameter, 150-250 m in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 V and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/sec) and efferent (0.7-8.8 m/sec) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.

bioengineering↗

bioRxiv2020

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

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.

bioengineering↗

bioRxiv2019

Bladder pressure encoding by near-independent fibre subpopulations - implications for decoding

ObjectiveWe aim at characterising the encoding of bladder pressure (intravesical pressure) by a population of sensory fibres. This research is motivated by the possibility to restore bladder function in elderly patients or after spinal cord injury using implanted devices, so called bioelectronic medicines. For these devices, nerve-based estimation of intravesical pressure can enable a personalized and on-demand stimulation paradigm, which will be more effective and efficient. In this context, a better understanding of the encoding strategies employed by the body might in the future be exploited by informed decoding algorithms that enable a precise and robust bladderpressure estimation. ApproachTo this end, we apply information theory to microelectrode-array recordings from the cat sacral dorsal root ganglion while filling the bladder, conduct surrogate data studies to augment the data we have, and finally decode pressure in a simple informed approach. Main resultsWe find an encoding scheme by different main bladder neuron types that we divide into three response types (slow tonic, phasic, and derivative fibres). We show that an encoding by different bladder neuron types, each represented by multiple cells, offers reliability through within-type redundancy and high information rates through near-independence of different types. Our subsequent decoding study shows a potentially more robust decoding from mean responses of homogeneous cell pools. SignificanceWe have here, for the first time, analysed the encoding of intravesical pressure by a population of sensory neurons in a principled way using information theory. We show that even a simple adapted decoder can exploit the redundancy in the population to be more robust against cell loss. This work thus paves the way towards principled encoding studies in the periphery and towards a new generation of informed peripheral nerve decoders for bioelectronic medicines.

bioengineering↗

bioRxiv2019

The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation

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.

microbiology↗

bioRxiv2019

Ultra-compliant carbon nanotube stretchable direct bladder interface

The bladder, stomach, intestines, heart, and lungs all move dynamically to achieve their purpose. A long-term implantable device that can attach onto an organ, sense its movement, and deliver current to modify the organ function would be useful in many therapeutic applications. The bladder, for example, is a smooth muscle organ that can suffer from incomplete contractions that result in urinary retention with patients requiring using catheterization. Those affected may benefit from a combination of strain sensor and electrical stimulator to better control bladder emptying. We describe the materials and design of such a device made from thin layer carbon nanotube (CNT) and Ecoflex 00-50 and demonstrate its function with in vivo feline bladders. During bench-top characterization, the resistive and capacitive sensors exhibited reliable output throughout 5,000 stretching cycles under physiology condition. In vivo measurement with piezoresistive device showed a high correlation between sensor resistance and volume. Stimulation driven from Pt-PDMS composite electrodes successfully induced bladder contraction. We present method for reliable connection and packaging of medical grade wire to the CNT device. This work is an important step toward the translation of low-durometer elastomers, stretchable CNT percolation and Pt-PDMS composite, which are ideal for large strain bioelectric applications to sense or modulate dynamic organ states.

bioengineering↗

bioRxiv2018

Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression

The ability to deliver flexible biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering. Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a three-dimensional diamond shuttle can be easily made with a vertical support to deliver ultra-compliant polymer microelectrodes (4.5 m thick) in-vivo through dura mater and thick epineurium. The diamond shuttle has 54% less cross-sectional area than an equivalently stiff silicon shuttle, which we simulated will result in a 37% reduction in blood vessel damage. We also discovered that higher frequency oscillation of the shuttle (200 Hz) significantly reduced tissue compression regardless of the insertion speed, while slow speeds also independently reduced tissue compression. Insertion and recording performance are demonstrated in rat and feline models, but the large design space of these tools are suitable for research in a variety of animal models and nervous system targets.

bioengineering↗