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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ItemOrientation pinwheels in primary visual cortex of a highly visual marsupial(AMER ASSOC ADVANCEMENT SCIENCE, 2022-09-30)Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and-pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.
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ItemAnalysis of extracellular spike waveforms and associated receptive fields of neurons in cat primary visual cortex(WILEY, 2021-04)KEY POINTS: Extracellular spikes recorded in the visual cortex (Area 17/18, V1) are commonly classified into either regular-spiking (RS) or fast-spiking (FS). Using multi-electrode arrays positioned in cat V1 and a broadband stimulus, we show that there is also a distinct class with positive-spiking (PS) waveforms. PS units were associated mainly with non-oriented receptive fields while RS and FS units had orientation-selective receptive fields. We suggest that PS units are recordings of axons originating from the thalamus. This conclusion was reinforced by our finding that we could record PS units after cortical silencing, but not record RS and FS units. The importance of our findings is that we were able to correlate spike shapes with receptive field characteristics with high precision using multi-electrode extracellular recording techniques. This allows considerable increases in the amount of information that can be extracted from future cortical experiments. ABSTRACT: Extracellular spike waveforms from recordings in the visual cortex have been classified into either regular-spiking (RS) or fast-spiking (FS) units. While both these types of spike waveforms are negative-dominant, we show that there are also distinct classes of spike waveforms in visual Area 17/18 (V1) of anaesthetised cats with positive-dominant waveforms, which are not regularly reported. The spatial receptive fields (RFs) of these different spike waveform types were estimated, which objectively revealed the existence of oriented and non-oriented RFs. We found that units with positive-dominant spikes, which have been associated with recordings from axons in the literature, had mostly non-oriented RFs (84%), which are similar to the centre-surround RFs observed in the dorsal lateral geniculate nucleus (dLGN). Thus, we hypothesise that these positive-dominant waveforms may be recordings from dLGN afferents. We recorded from V1 before and after the application of muscimol (a cortical silencer) and found that the positive-dominant spikes (PS) remained while the RS and FS cells did not. We also noted that the PS units had spiking characteristics normally associated with dLGN units (i.e. higher response spike rates, lower response latencies and higher proportion of burst spikes). Our findings show quantitatively that it is possible to correlate the RF properties of cortical neurons with particular spike waveforms. This has implications for how extracellular recordings should be interpreted and complex experiments can now be contemplated that would have been very challenging previously, such as assessing the feedforward connectivity between brain areas in the same location of cortical tissue.
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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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ItemOptical stimulation of neural tissue(INST ENGINEERING TECHNOLOGY-IET, 2020-06)Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.
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ItemAdaptive Surround Modulation of MT Neurons: A Computational Model(FRONTIERS MEDIA SA, 2020-10-26)The classical receptive field (CRF) of a spiking visual neuron is defined as the region in the visual field that can generate spikes when stimulated by a visual stimulus. Many visual neurons also have an extra-classical receptive field (ECRF) that surrounds the CRF. The presence of a stimulus in the ECRF does not generate spikes but rather modulates the response to a stimulus in the neuron's CRF. Neurons in the primate Middle Temporal (MT) area, which is a motion specialist region, can have directionally antagonistic or facilitatory surrounds. The surround's effect switches between directionally antagonistic or facilitatory based on the characteristics of the stimulus, with antagonistic effects when there are directional discontinuities but facilitatory effects when there is directional coherence. Here, we present a computational model of neurons in area MT that replicates this observation and uses computational building blocks that correlate with observed cell types in the visual pathways to explain the mechanism of this modulatory effect. The model shows that the categorization of MT neurons based on the effect of their surround depends on the input stimulus rather than being a property of the neurons. Also, in agreement with neurophysiological findings, the ECRFs of the modeled MT neurons alter their center-surround interactions depending on image contrast.
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ItemOrigins of Functional Organization in the Visual Cortex(FRONTIERS MEDIA SA, 2020-03-03)How are the complex maps for orientation selectivity (OS) created in the primary visual cortex (V1)? Rodents and rabbits have a random distribution of OS preferences across V1 while in cats, ferrets, and all primates cells with similar OS preferences cluster together into relatively wide cortical columns. Given other clear similarities in the organization of the visual pathways, why is it that maps coding OS preferences are so radically different? Prominent models have been created of cortical OS mapping that incorporate Hebbian plasticity, intracortical interactions, and the properties of growing axons. However, these models suggest that the maps arise primarily through intracortical interactions. Here we focus on several other features of the visual system and brain that may influence V1 structure. These are: eye divergence, the total number of cells in V1, the thalamocortical networks, the topography of the retina and phylogeny. We outline the evidence for and against these factors contributing to map formation. One promising theory is that the central-to-peripheral ratio (CP ratio) of retinal cell density can be used to predict whether or not a species has pinwheel maps. Animals with high CP ratios (>7) have orientation columns while those with low CP ratios (<4) have random OS maps. The CP ratio is related to the total number of cells in cortex, which also appears to be a reasonable contributing factor. However, while these factors correlate with map structure to some extent, there is a gray area where certain species do not fit elegantly into the theory. A problem with the existing literature is that OS maps have been investigated in only a small number of mammals, from a small fraction of the mammalian phylogenetic tree. We suggest four species (agouti, fruit bat, sheep, and wallaby) that have a range of interesting characteristics, which sit at intermediate locations between primates and rodents, that make them good targets for filling in the missing gaps in the literature. We make predictions about the map structures of these species based on the organization of their brains and visual systems and, in doing so, set possible paths for future research.
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ItemMechanisms of Feature Selectivity and Invariance in Primary Visual Cortex.(Oxford University Press (OUP), 2020-09)Visual object identification requires both selectivity for specific visual features that are important to the object's identity and invariance to feature manipulations. For example, a hand can be shifted in position, rotated, or contracted but still be recognized as a hand. How are the competing requirements of selectivity and invariance built into the early stages of visual processing? Typically, cells in the primary visual cortex are classified as either simple or complex. They both show selectivity for edge-orientation but complex cells develop invariance to edge position within the receptive field (spatial phase). Using a data-driven model that extracts the spatial structures and nonlinearities associated with neuronal computation, we quantitatively describe the balance between selectivity and invariance in complex cells. Phase invariance is frequently partial, while invariance to orientation and spatial frequency are more extensive than expected. The invariance arises due to two independent factors: (1) the structure and number of filters and (2) the form of nonlinearities that act upon the filter outputs. Both vary more than previously considered, so primary visual cortex forms an elaborate set of generic feature sensitivities, providing the foundation for more sophisticated object processing.