Biomedical Engineering - Research Publications
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ItemQuantifying visual acuity for pre-clinical testing of visual prostheses(IOP Publishing Ltd, 2023-02-01)Objective.Visual prostheses currently restore only limited vision. More research and pre-clinical work are required to improve the devices and stimulation strategies that are used to induce neural activity that results in visual perception. Evaluation of candidate strategies and devices requires an objective way to convert measured and modelled patterns of neural activity into a quantitative measure of visual acuity.Approach.This study presents an approach that compares evoked patterns of neural activation with target and reference patterns. A d-prime measure of discriminability determines whether the evoked neural activation pattern is sufficient to discriminate between the target and reference patterns and thus provides a quantified level of visual perception in the clinical Snellen and MAR scales. The magnitude of the resulting value was demonstrated using scaled standardized 'C' and 'E' optotypes.Main results.The approach was used to assess the visual acuity provided by two alternative stimulation strategies applied to simulated retinal implants with different electrode pitch configurations and differently sized spreads of neural activity. It was found that when there is substantial overlap in neural activity generated by different electrodes, an estimate of acuity based only upon electrode pitch is incorrect; our proposed method gives an accurate result in both circumstances.Significance.Quantification of visual acuity using this approach in pre-clinical development will allow for more rapid and accurate prototyping of improved devices and neural stimulation strategies.
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ItemA comparison of open-loop and closed-loop stimulation strategies to control excitation of retinal ganglion cells(Elsevier, 2014-11-01)Currently, open-loop stimulation strategies are prevalent in medical bionic devices. These strategies involve setting electrical stimulation that does not change in response to neural activity. We investigate through simulation the advantages of using a closed-loop strategy that sets stimulation level based on continuous measurement of the level of neural activity. We propose a model-based controller design to control activation of retinal neurons. To deal with the lack of controllability and observability of the whole system, we use Kalman decomposition and control only the controllable and observable part. We show that the closed-loop controller performs better than the open-loop controller when perturbations are introduced into the system. We envisage that our work will give rise to more investigations of the closed-loop techniques in basic neuroscience research and in clinical applications of medical bionics.
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ItemNeural activity shaping utilizing a partitioned target pattern(IOP PUBLISHING LTD, 2021-08)Electrical stimulation of neural tissue is used in both clinical and experimental devices to evoke a desired spatiotemporal pattern of neural activity. These devices induce a local field that drives neural activation, referred to as an activating function or generator signal. In visual prostheses, the spread of generator signal from each electrode within the neural tissue results in a spread of visual perception, referred to as a phosphene.Objective.In cases where neighbouring phosphenes overlap, it is desirable to use current steering or neural activity shaping strategies to manipulate the generator signal between the electrodes to provide greater control over the total pattern of neural activity. Applying opposite generator signal polarities in neighbouring regions of the retina forces the generator signal to pass through zero at an intermediate point, thus inducing low neural activity that may be perceived as a high-contrast line. This approach provides a form of high contrast visual perception, but it requires partitioning of the target pattern into those regions that use positive or negative generator signals. This discrete optimization is an NP-hard problem that is subject to being trapped in detrimental local minima.Approach.This investigation proposes a new partitioning method using image segmentation to determine the most beneficial positive and negative generator signal regions. Utilizing a database of 1000 natural images, the method is compared to alternative approaches based upon the mean squared error of the outcome.Main results.Under nominal conditions and with a set computation limit, partitioning provided improvement for 32% of these images. This percentage increased to 89% when utilizing image pre-processing to emphasize perceptual features of the images. The percentage of images that were dealt with most effectively with image segmentation increased as lower computation limits were imposed on the algorithms.Significance.These results provide a new method to increase the resolution of neural stimulating arrays and thus improve the experience of visual prosthesis users.
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ItemLearning receptive field properties of complex cells in V1(PUBLIC LIBRARY SCIENCE, 2021-03)There are two distinct classes of cells in the primary visual cortex (V1): simple cells and complex cells. One defining feature of complex cells is their spatial phase invariance; they respond strongly to oriented grating stimuli with a preferred orientation but with a wide range of spatial phases. A classical model of complete spatial phase invariance in complex cells is the energy model, in which the responses are the sum of the squared outputs of two linear spatially phase-shifted filters. However, recent experimental studies have shown that complex cells have a diverse range of spatial phase invariance and only a subset can be characterized by the energy model. While several models have been proposed to explain how complex cells could learn to be selective to orientation but invariant to spatial phase, most existing models overlook many biologically important details. We propose a biologically plausible model for complex cells that learns to pool inputs from simple cells based on the presentation of natural scene stimuli. The model is a three-layer network with rate-based neurons that describes the activities of LGN cells (layer 1), V1 simple cells (layer 2), and V1 complex cells (layer 3). The first two layers implement a recently proposed simple cell model that is biologically plausible and accounts for many experimental phenomena. The neural dynamics of the complex cells is modeled as the integration of simple cells inputs along with response normalization. Connections between LGN and simple cells are learned using Hebbian and anti-Hebbian plasticity. Connections between simple and complex cells are learned using a modified version of the Bienenstock, Cooper, and Munro (BCM) rule. Our results demonstrate that the learning rule can describe a diversity of complex cells, similar to those observed experimentally.
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ItemThe effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation results(SPRINGER, 2014-04)Retinal ganglion cells (RGCs) display differences in their morphology and intrinsic electrophysiology. The goal of this study is to characterize the ionic currents that explain the behavior of ON and OFF RGCs and to explore if all morphological types of RGCs exhibit the phenomena described in electrophysiological data. We extend our previous single compartment cell models of ON and OFF RGCs to more biophysically realistic multicompartment cell models and investigate the effect of cell morphology on intrinsic electrophysiological properties. The membrane dynamics are described using the Hodgkin - Huxley type formalism. A subset of published patch-clamp data from isolated intact mouse retina is used to constrain the model and another subset is used to validate the model. Two hundred morphologically distinct ON and OFF RGCs are simulated with various densities of ionic currents in different morphological neuron compartments. Our model predicts that the differences between ON and OFF cells are explained by the presence of the low voltage activated calcium current in OFF cells and absence of such in ON cells. Our study shows through simulation that particular morphological types of RGCs are capable of exhibiting the full range of phenomena described in recent experiments. Comparisons of outputs from different cells indicate that the RGC morphologies that best describe recent experimental results are ones that have a larger ratio of soma to total surface area.
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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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ItemGlobal activity shaping strategies for a retinal implant(IOP Publishing, 2019-09-18)Objective. Retinal prostheses provide visual perception via electrical stimulation of the retina using an implanted array of electrodes. The retinal activation resulting from each electrode is not point-like; instead each electrode introduces a spread of retinal activation that may overlap with activations from other electrodes. With most conventional stimulation strategies this overlap leads to image blur. Here we propose a 'shaping' algorithm that uses multiple electrodes to manipulate the current between electrodes in a desired way. Approach. We assume a forward model for the conversion of electrode strengths to retinal activation. Three alternative global shaping algorithms are developed by calculating reverse models under different assumptions: linear inversion using singular value decomposition to produce the pseudoinverse, a linearly constrained quadratic program, and a binary quadratic program to partition the target pattern. The algorithms were assessed using both the mean squared error between the resulting images and desired images, as well as their adherence to the maximum allowed electrode currents. Main results. Under wide activation spreads the linear inversion algorithm gave improved solutions but faced two limitations: under low-noise conditions the electrode amplitudes exceeded their set limit; the set of solutions did not include the possibility of using negative local currents to induce retinal activation. The linearly constrained quadratic program and binary quadratic program respectively addressed these problems, but required much greater computation time. Significance. This provides a framework for improving the resolution of future retinal implants, especially those with high density electrode arrays.
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ItemToward a Biologically Plausible Model of LGN-V1 Pathways Based on Efficient Coding(Frontiers Media, 2019-03-14)Increasing evidence supports the hypothesis that the visual system employs a sparse code to represent visual stimuli, where information is encoded in an efficient way by a small population of cells that respond to sensory input at a given time. This includes simple cells in primary visual cortex (V1), which are defined by their linear spatial integration of visual stimuli. Various models of sparse coding have been proposed to explain physiological phenomena observed in simple cells. However, these models have usually made the simplifying assumption that inputs to simple cells already incorporate linear spatial summation. This overlooks the fact that these inputs are known to have strong non-linearities such the separation of ON and OFF pathways, or separation of excitatory and inhibitory neurons. Consequently thesemodels ignore a range of important experimental phenomena that are related to the emergence of linear spatial summation from non-linear inputs, such as segregation of ON and OFF sub-regions of simple cell receptive fields, the push-pull effect of excitation and inhibition, and phase-reversed cortico-thalamic feedback. Here, we demonstrate that a two-layer model of the visual pathway from the lateral geniculate nucleus to V1 that incorporates these biological constraints on the neural circuits and is based on sparse coding can account for the emergence of these experimental phenomena, diverse shapes of receptive fields and contrast invariance of orientation tuning of simple cells when the model is trained on natural images. The model suggests that sparse coding can be implemented by the V1 simple cells using neural circuits with a simple biologically plausible architecture.
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ItemPattern Motion Processing by MT Neurons(Frontiers Media, 2019-06-21)Based on stimulation with plaid patterns, neurons in the Middle Temporal (MT) area of primate visual cortex are divided into two types: pattern and component cells. The prevailing theory suggests that pattern selectivity results from the summation of the outputs of component cells as part of a hierarchical visual pathway. We present a computational model of the visual pathway from primary visual cortex (V1) to MT that suggests an alternate model where the progression from component to pattern selectivity is not required. Using standard orientation-selective V1 cells, end-stopped V1 cells, and V1 cells with extra-classical receptive fields (RFs) as inputs to MT, the model shows that the degree of pattern or component selectivity in MT could arise from the relative strengths of the three V1 input types. Dominance of end-stopped V1 neurons in the model leads to pattern selectivity in MT, while dominance of V1 cells with extra-classical RFs result in component selectivity. This model may assist in designing experiments to further understand motion processing mechanisms in primate MT.
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ItemElectrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons(PUBLIC LIBRARY SCIENCE, 2018-02)Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.