Anatomy and Neuroscience - Research Publications

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    Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces
    Eiber, CD ; Payne, SC ; Biscola, NP ; Havton, LA ; Keast, JR ; Osborne, PB ; Fallon, JB (IOP Publishing Ltd, 2021-12)
    Objective.Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and predictability of neural interface performance. Here we use computational models of rat visceral nerve to predict how neuroanatomical variability could affect both electrical stimulation and recording with an experimental planar neural interface.Approach.We developed a hybrid computational pipeline,VisceralNerveEnsembleRecording andStimulation (ViNERS), to couple finite-element modelling of extracellular electrical fields with biophysical simulations of individual axons. Anatomical properties of fascicles and axons in rat pelvic and vagus nerves were measured or obtained from public datasets. To validate ViNERS, we simulated pelvic nerve stimulation and recording with an experimental four-electrode planar array.Main results.Axon diameters measured from pelvic nerve were used to model a population of myelinated and unmyelinated axons and simulate recordings of electrically evoked single-unit field potentials (SUFPs). Across visceral nerve fascicles of increasing size, our simulations predicted an increase in stimulation threshold and a decrease in SUFP amplitude. Simulated threshold changes were dominated by changes in perineurium thickness, which correlates with fascicle diameter. We also demonstrated that ViNERS could simulate recordings of electrically-evoked compound action potentials (ECAPs) that were qualitatively similar to pelvic nerve recording made with the array used for simulation.Significance.We introduce ViNERS as a new open-source computational tool for modelling large-scale stimulation and recording from visceral nerves. ViNERS predicts how neuroanatomical variation in rat pelvic nerve affects stimulation and recording with an experimental planar electrode array. We show ViNERS can simulate ECAPS that capture features of our recordings, but our results suggest the underlying NEURON models need to be further refined and specifically adapted to accurately simulate visceral nerve axons.
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    Rapid Analysis of Visual Receptive Fields by Iterative Tomography.
    Eiber, CD ; Huang, JY ; Chen, SC ; Zeater, N ; Pietersen, ANJ ; Protti, DA ; Martin, PR (Society for Neuroscience, 2021)
    Many receptive fields in the early visual system show standard (center-surround) structure and can be analyzed using simple drifting patterns and a difference-of-Gaussians (DoG) model, which treats the receptive field as a linear filter of the visual image. But many other receptive fields show nonlinear properties such as selectivity for direction of movement. Such receptive fields are typically studied using discrete stimuli (moving or flashed bars and edges) and are modelled according to the features of the visual image to which they are most sensitive. Here, we harness recent advances in tomographic image analysis to characterize rapidly and simultaneously both the linear and nonlinear components of visual receptive fields. Spiking and intracellular voltage potential responses to briefly flashed bars are analyzed using non-negative matrix factorization (NNMF) and iterative reconstruction tomography (IRT). The method yields high-resolution receptive field maps of individual neurons and neuron ensembles in primate (marmoset, both sexes) lateral geniculate and rodent (mouse, male) retina. We show that the first two IRT components correspond to DoG-equivalent center and surround of standard [magnocellular (M) and parvocellular (P)] receptive fields in primate geniculate. The first two IRT components also reveal the spatiotemporal receptive field structure of nonstandard (on/off-rectifying) receptive fields. In rodent retina we combine NNMF-IRT with patch-clamp recording and dye injection to directly map spatial receptive fields to the underlying anatomy of retinal output neurons. We conclude that NNMF-IRT provides a rapid and flexible framework for study of receptive fields in the early visual system.
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    Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array
    Payne, SC ; Wiedmann, NM ; Eiber, CD ; Wong, AW ; Senn, P ; Osborne, PB ; Keast, JR ; Fallon, JB (FRONTIERS MEDIA SA, 2020-12-17)
    Bioelectronic medical devices are well established and widely used in the treatment of urological dysfunction. Approved targets include the sacral S3 spinal root and posterior tibial nerve, but an alternate target is the group of pelvic splanchnic nerves, as these contain sacral visceral sensory and autonomic motor pathways that coordinate storage and voiding functions of the bladder. Here, we developed a device suitable for long-term use in an awake rat model to study electrical neuromodulation of the pelvic nerve (homolog of the human pelvic splanchnic nerves). In male Sprague-Dawley rats, custom planar four-electrode arrays were implanted over the distal end of the pelvic nerve, close to the major pelvic ganglion. Electrically evoked compound action potentials (ECAPs) were reliably detected under anesthesia and in chronically implanted, awake rats up to 8 weeks post-surgery. ECAP waveforms showed three peaks, with latencies that suggested electrical stimulation activated several subpopulations of myelinated A-fiber and unmyelinated C-fiber axons. Chronic implantation of the array did not impact on voiding evoked in awake rats by continuous cystometry, where void parameters were comparable to those published in naïve rats. Electrical stimulation with chronically implanted arrays also induced two classes of bladder pressure responses detected by continuous flow cystometry in awake rats: voiding contractions and non-voiding contractions. No evidence of tissue pathology produced by chronically implanted arrays was detected by immunohistochemical visualization of markers for neuronal injury or noxious spinal cord activation. These results demonstrate a rat pelvic nerve electrode array that can be used for preclinical development of closed loop neuromodulation devices targeting the pelvic nerve as a therapy for neuro-urological dysfunction.
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    Simulating bidirectional peripheral neural interfaces in EIDORS
    Eiber, CD ; Keast, JR ; Osborne, PB (IEEE, 2020-01-01)
    Bioelectronic neural interfaces that deliver adaptive therapeutic stimulation in an intelligent manner must be able to sense and stimulate activity within the same nerve. Existing minimally-invasive peripheral neural interfaces can provide a read-out of the aggregate level of activity via electrical recordings of nerve activity, but these recordings are limited in terms of their specificity. Computational simulations can provide fine-grained insight into the contributions of different neural populations to the extracellular recording, but integration of the signals from individual nerve fibers requires knowledge of spread of current in the complex (heterogenous, anisotropic) extracellular space. We have developed a model which uses the open-source EIDORS package for extracellular stimulation and recording in the pelvic nerve. The pelvic nerve is the primary source of autonomic innervation to the pelvic organs, and a prime target for electrical stimulation to treat a variety of voiding disorders. We simulated recordings of spontaneous and electrically-evoked activity using biophysical models for myelinated and unmyelinated axons. As expected, stimulus thresholds depended strongly on both fibre type and electrode-fibre distance. In conclusion, EIDORS can be used to accurately simulate extracellular recording in complex, heterogenous neural geometries.
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    Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces
    Eiber, CD ; Delbeke, J ; Cardoso, J ; de Neeling, M ; John, SE ; Lee, CW ; Skefos, J ; Sun, A ; Prodanov, D ; McKinney, Z (Cold Spring Harbor Laboratory, 2021)
    The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives. Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR). Index Terms— Neurotechnology, reproducibility, scientific reporting, standardization, bioelectronic medicine Impact Statement— This work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.