Biology subjects

Madden, L. R.

Publications and source records attributed to Madden, L. R..

3 recordsLinked to original sources

bioRxiv2024

Physiological activity within peripheral nerves influences neural output in response to electrical stimulation: an in vivo study

Neuromodulation therapies are often applied to peripheral nerves. These nerves can have physiological activity that interacts with the activity evoked by electrical stimulation, potentially influencing targeted neural output and clinical outcomes. Our goal was to quantify changes in sensory neural unit activity in response to variations in electrical stimulation frequency and amplitude. In a feline model, we applied cutaneous brushing to evoke pudendal nerve afferent activity with and without electrical stimulation via a pudendal nerve cuff electrode. We recorded neural output with microelectrode arrays implanted in ipsilateral sacral dorsal root ganglia (DRG). Combined inter-spike interval distributions for all DRG units showed ranges of flattening, increases, and shifts in response to electrical stimulation. These distributions and changes within them due to electrical stimulation were largely driven by a select few units. Mixed-effects models revealed that quicker firing units generally decreased in firing rate in response to electrical stimulation and, conversely, slower firing units increased in firing rate. A units underlying firing rate also drove the magnitude of change in mean output firing rate in response to stimulation. Further, the models reported a small, negative correlation between the output mean unit firing rate and the applied electrical stimulation frequency. These results demonstrate the potential impact of electrical stimulation on underlying neural firing activity and output. Peripheral neuromodulation may normalize abnormal firing patterns in nerves contributing to pathological disorders or alter unrelated physiological activity in off-target neurons. These factors should be considered when selecting neuromodulation settings in animal subjects and human patients.

neuroscience↗

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↗

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↗