Optometry and Vision Sciences - Research Publications
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ItemNo Preview AvailablePreferential modulation of individual retinal ganglion cells by electrical stimulation(IOP Publishing Ltd, 2022-08-01)Objective.Retinal prostheses have had limited success in vision restoration through electrical stimulation of surviving retinal ganglion cells (RGCs) in the degenerated retina. This is partly due to non-preferential stimulation of all RGCs near a single stimulating electrode, which include cells that conflict in their response properties and their contribution to visiual processing. Our study proposes a stimulation strategy to preferentially stimulate individual RGCs based on their temporal electrical receptive fields (tERFs).Approach.We recorded the responses of RGCs using whole-cell patch clamping and demonstrated the stimulation strategy, first using intracellular stimulation, then via extracellular stimulation.Main results. We successfully reconstructed the tERFs according to the RGC response to Gaussian white noise current stimulation. The characteristics of the tERFs were extracted and compared based on the morphological and light response types of the cells. By re-delivering stimulation trains that were composed of the tERFs obtained from different cells, we could preferentially stimulate individual RGCs as the cells showed lower activation thresholds to their own tERFs.Significance.This proposed stimulation strategy implemented in the next generation of recording and stimulating retinal prostheses may improve the quality of artificial vision.
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ItemNo Preview AvailableActivity of Retinal Neurons Can Be Modulated by Tunable Near-Infrared Nanoparticle Sensors.(American Chemical Society (ACS), 2023-02-14)The vision of patients rendered blind by photoreceptor degeneration can be partially restored by exogenous stimulation of surviving retinal ganglion cells (RGCs). Whereas conventional electrical stimulation techniques have failed to produce naturalistic visual percepts, nanoparticle-based optical sensors have recently received increasing attention as a means to artificially stimulate the RGCs. In particular, nanoparticle-enhanced infrared neural modulation (NINM) is a plasmonically mediated photothermal neuromodulation technique that has a demonstrated capacity for both stimulation and inhibition, which is essential for the differential modulation of ON-type and OFF-type RGCs. Gold nanorods provide tunable absorption through the near-infrared wavelength window, which reduces interference with any residual vision. Therefore, NINM may be uniquely well-suited to retinal prosthesis applications but, to our knowledge, has not previously been demonstrated in RGCs. In the present study, NINM laser pulses of 100 μs, 500 μs and 200 ms were applied to RGCs in explanted rat retinae, with single-cell responses recorded via patch-clamping. The shorter laser pulses evoked robust RGC stimulation by capacitive current generation, while the long laser pulses are capable of inhibiting spontaneous action potentials by thermal block. Importantly, an implicit bias toward OFF-type inhibition is observed, which may have important implications for the feasibility of future high-acuity retinal prosthesis design based on nanoparticle sensors.
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ItemNo Preview AvailableEnhanced effective diffusion in sub-wavelength, axon-scale microchannels using surface acoustic waves(AIP Publishing, 2023-03)Excitation using surface acoustic waves (SAW) has demonstrated efficacy in improving microscale particle/chemical transport due to its ability to generate microscale wavelengths. However, the effects of acoustic stimulation on transport processes along the length of sub-wavelength microchannels and their underlying mechanisms, essential for long-range transport, have not been examined in detail. In this work, we investigate diffusion along the length of subwavelength microchannels using experimental and simulation approaches, demonstrating enhanced transport under SAW excitation. The microchannel-based enhanced diffusion mechanisms are further studied by investigating the acoustic pressure and streaming fields, finding that the degree of enhancement is a function of applied power, microchannel dimensions, and viscosity. This microchannel-based diffusion enhancement approach is applicable to microfluidic and biomedical microscale transport enhancement, with the findings here being relevant to acoustic-based micro-mixing and neurodegenerative therapies.
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ItemAdvances in Carbon-Based Microfiber Electrodes for Neural Interfacing(FRONTIERS MEDIA SA, 2021-04-12)Neural interfacing devices using penetrating microelectrode arrays have emerged as an important tool in both neuroscience research and medical applications. These implantable microelectrode arrays enable communication between man-made devices and the nervous system by detecting and/or evoking neuronal activities. Recent years have seen rapid development of electrodes fabricated using flexible, ultrathin carbon-based microfibers. Compared to electrodes fabricated using rigid materials and larger cross-sections, these microfiber electrodes have been shown to reduce foreign body responses after implantation, with improved signal-to-noise ratio for neural recording and enhanced resolution for neural stimulation. Here, we review recent progress of carbon-based microfiber electrodes in terms of material composition and fabrication technology. The remaining challenges and future directions for development of these arrays will also be discussed. Overall, these microfiber electrodes are expected to improve the longevity and reliability of neural interfacing devices.
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ItemHigh Fidelity Bidirectional Neural Interfacing with Carbon Fiber Microelectrodes Coated with Boron-Doped Carbon Nanowalls: An Acute Study(WILEY-V C H VERLAG GMBH, 2020-12)Abstract Implantable electrodes that can communicate with a small, selective group of neurons via both neural stimulation and recording are critical for the development of advanced neuroprosthetic devices. Microfiber electrodes with neuron‐scale cross‐sections have the potential to improve the spatial resolution for both stimulation and recording, while minimizing the chronic inflammation response after implantation. In this work, glass insulated microfiber electrodes are fabricated by coating carbon fibers with boron‐doped carbon nanowalls. The coating significantly improves the electrochemical properties of carbon fibers, leading to a charge injection capacity of 7.82 ± 0.35 mC cm−2, while retaining good flexibility, stability and biocompatibility. When used for neural interfacing, the coated microelectrodes successfully elicit localized stimulation responses in explanted retina, and are also able to detect signals from single neurons, in vivo with a signal‐to‐noise ratio as high as 6.7 in an acute study. This is the first report of using carbon nanowall coated carbon fibers for neural interfacing.
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ItemMechanisms and Applications of Neuromodulation Using Surface Acoustic Waves-A Mini-Review(FRONTIERS MEDIA SA, 2021-01-27)The study of neurons is fundamental for basic neuroscience research and treatment of neurological disorders. In recent years ultrasound has been increasingly recognized as a viable method to stimulate neurons. However, traditional ultrasound transducers are limited in the scope of their application by self-heating effects, limited frequency range and cavitation effects during neuromodulation. In contrast, surface acoustic wave (SAW) devices, which are producing wavemodes with increasing application in biomedical devices, generate less self-heating, are smaller and create less cavitation. SAW devices thus have the potential to address some of the drawbacks of traditional ultrasound transducers and could be implemented as miniaturized wearable or implantable devices. In this mini review, we discuss the potential mechanisms of SAW-based neuromodulation, including mechanical displacement, electromagnetic fields, thermal effects, and acoustic streaming. We also review the application of SAW actuation for neuronal stimulation, including growth and neuromodulation. Finally, we propose future directions for SAW-based neuromodulation.
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ItemHybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing(Elsevier, 2020-02-01)Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.
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ItemStimulation Strategies for Improving the Resolution of Retinal Prostheses.(Frontiers Media, 2020-03-26)Electrical stimulation using implantable devices with arrays of stimulating electrodes is an emerging therapy for neurological diseases. The performance of these devices depends greatly on their ability to activate populations of neurons with high spatiotemporal resolution. To study electrical stimulation of populations of neurons, retina serves as a useful model because the neural network is arranged in a planar array that is easy to access. Moreover, retinal prostheses are under development to restore vision by replacing the function of damaged light sensitive photoreceptors, which makes retinal research directly relevant for curing blindness. Here we provide a progress review on stimulation strategies developed in recent years to improve the resolution of electrical stimulation in retinal prostheses. We focus on studies performed with explanted retinas, in which electrophysiological techniques are the most advanced. We summarize achievements in improving the spatial and temporal resolution of electrical stimulation of the retina and methods to selectively stimulate neurons with different visual functions. Future directions for retinal prostheses development are also discussed, which could provide insights for other types of neuromodulatory devices in which high-resolution electrical stimulation is required.