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Creators/Authors contains: "Weiland, James"

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  1. To broaden efforts for improving diversity, equity, and inclusion (DEI) in biomedical engineering (BME) education—a key area of emphasis is the integration of inclusive teaching practices. While BME faculty generally support these efforts, translating support into action remains challenging. This project aimed to address this need through a 3-phase inclusive teaching training, consisting of graduate students, faculty, and engineering education consultants. In Phase I, graduate students and faculty participated in a 6-week learning community on inclusive teaching (Foundational Learning). In Phase II, graduate students were paired with faculty to modify or develop new inclusive teaching materials to be integrated into a BME course (Experiential Learning). Phase III was the implementation of these materials. To assess Phases I & II, graduate student participants reflected on their experiences on the project. To assess Phase III, surveys were administered to students in IT-BME-affiliated courses as well as those taking other BME-related courses. Phases I & II: graduate students responded positively to the opportunity to engage in this inclusive teaching experiential learning opportunity. Phase III: survey results indicated that the incorporation of inclusive teaching practices in BME courses enhanced the student learning experience. The IT-BME project supported graduate students and faculty in learning about, creating, and implementing inclusive teaching practices in a collaborative and supportive environment. This project will serve to both train the next class of instructors and use their study of inclusive teaching concepts to facilitate the creation of ideas and materials that will benefit the BME curriculum and students. 
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  2. Abstract Shape-morphable electrode arrays can form 3D surfaces to conform to complex neural anatomy and provide consistent positioning needed for next-generation neural interfaces. Retinal prostheses need a curved interface to match the spherical eye and a coverage of several cm to restore peripheral vision. We fabricated a full-field array that can (1) cover a visual field of 57° based on electrode position and of 113° based on the substrate size; (2) fold to form a compact shape for implantation; (3) self-deploy into a curvature fitting the eye after implantation. The full-field array consists of multiple polymer layers, specifically, a sandwich structure of elastomer/polyimide-based-electrode/elastomer, coated on one side with hydrogel. Electrodeposition of high-surface-area platinum/iridium alloy significantly improved the electrical properties of the electrodes. Hydrogel over-coating reduced electrode performance, but the electrodes retained better properties than those without platinum/iridium. The full-field array was rolled into a compact shape and, once implanted into ex vivo pig eyes, restored to a 3D curved surface. The full-field retinal array provides significant coverage of the retina while allowing surgical implantation through an incision 33% of the final device diameter. The shape-changing material platform can be used with other neural interfaces that require conformability to complex neuroanatomy. 
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  3. Current standards for safe delivery of electrical stimulation to the central nervous system are based on foundational studies which examined post-mortem tissue for histological signs of damage. This set of observations and the subsequently proposed limits to safe stimulation, termed the “Shannon limits,” allow for a simple calculation (using charge per phase and charge density) to determine the intensity of electrical stimulation that can be delivered safely to brain tissue. In the three decades since the Shannon limits were reported, advances in molecular biology have allowed for more nuanced and detailed approaches to be used to expand current understanding of the physiological effects of stimulation. Here, we demonstrate the use of spatial transcriptomics (ST) in an exploratory investigation to assess the biological response to electrical stimulation in the brain. Electrical stimulation was delivered to the rat visual cortex with either acute or chronic electrode implantation procedures. To explore the influence of device type and stimulation parameters, we used carbon fiber ultramicroelectrode arrays (7 μm diameter) and microwire electrode arrays (50 μm diameter) delivering charge and charge density levels selected above and below reported tissue damage thresholds (range: 2–20 nC, 0.1–1 mC/cm 2 ). Spatial transcriptomics was performed using Visium Spatial Gene Expression Slides (10x Genomics, Pleasanton, CA, United States), which enabled simultaneous immunohistochemistry and ST to directly compare traditional histological metrics to transcriptional profiles within each tissue sample. Our data give a first look at unique spatial patterns of gene expression that are related to cellular processes including inflammation, cell cycle progression, and neuronal plasticity. At the acute timepoint, an increase in inflammatory and plasticity related genes was observed surrounding a stimulating electrode compared to a craniotomy control. At the chronic timepoint, an increase in inflammatory and cell cycle progression related genes was observed both in the stimulating vs. non-stimulating microwire electrode comparison and in the stimulating microwire vs. carbon fiber comparison. Using the spatial aspect of this method as well as the within-sample link to traditional metrics of tissue damage, we demonstrate how these data may be analyzed and used to generate new hypotheses and inform safety standards for stimulation in cortex. 
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  4. Abstract Objective.Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship.Approach.Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.8µm diameter) carbon fiber electrodes and the positions of surrounding neurons. We implanted male rats with carbon fiber electrode arrays for 6 or 12+ weeks targeting layer V motor cortex. After explanting the arrays, we immunostained the implant site and localized putative recording site tips with subcellular-cellular resolution. We then 3D segmented neuron somata within a 50µm radius from implanted tips to measure neuron positions and health and compare to healthy cortex with symmetric stereotaxic coordinates.Main results.Immunostaining of astrocyte, microglia, and neuron markers confirmed that overall tissue health was indicative of high biocompatibility near the tips. While neurons near implanted carbon fibers were stretched, their number and distribution were similar to hypothetical fibers placed in healthy contralateral brain. Such similar neuron distributions suggest that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated the prediction of spikes produced by nearby neurons using a simple point source model fit using recorded electrophysiology and the mean positions of the nearest neurons observed in histology. Comparing spike amplitudes suggests that the radius at which single units can be distinguished from others is near the fourth closest neuron (30.7 ± 4.6µm, X ˉ ± S) in layer V motor cortex.Significance.Collectively, these data and simulations provide the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting. 
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  5. Abstract Objective. To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8 µ m-diameter electrodes that can be assembled into dense arrays (pitches ⩾ 80 µ m). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recordings both acutely and chronically in neural tissue in vivo (e.g. rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation. Approach. We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine mollusk Aplysia californica . Neuron cell bodies in Aplysia range from 30 µ m to over 250 µ m. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron’s cell body with both electrodes and connecting them to a DC coupled amplifier. Main results. We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes. Significance. The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics. 
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  6. null (Ed.)
    Direct fabrication of a three-dimensional (3D) structure using soft materials has been challenging. The hybrid bilayer is a promising approach to address this challenge because of its programable shape-transformation ability when responding to various stimuli. The goals of this study are to experimentally and theoretically establish a rational design principle of a hydrogel/elastomer bilayer system and further optimize the programed 3D structures that can serve as substrates for multi-electrode arrays. The hydrogel/elastomer bilayer consists of a hygroscopic polyacrylamide (PAAm) layer cofacially laminated with a water-insensitive polydimethylsiloxane (PDMS) layer. The asymmetric volume change in the PAAm hydrogel can bend the bilayer into a curvature. We manipulate the initial monomer concentrations of the pre-gel solutions of PAAm to experimentally and theoretically investigate the effect of intrinsic mechanical properties of the hydrogel on the resulting curvature. By using the obtained results as a design guideline, we demonstrated stimuli-responsive transformation of a PAAm/PDMS flower-shaped bilayer from a flat bilayer film to a curved 3D structure that can serve as a substrate for a wide-field retinal electrode array. 
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