Biomedical Engineering - Research Publications

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    A comparison of open-loop and closed-loop stimulation strategies to control excitation of retinal ganglion cells
    Kameneva, T ; Zarelli, D ; Nesic, D ; Grayden, DB ; Burkitt, AN ; Meffin, H (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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    The effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation results
    Maturana, MI ; Kameneva, T ; Burkitt, AN ; Meffin, H ; Grayden, DB (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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    Coexistence of Reward and Unsupervised Learning During the Operant Conditioning of Neural Firing Rates
    Kerr, RR ; Grayden, DB ; Thomas, DA ; Gilson, M ; Burkitt, AN ; Cymbalyuk, G (PUBLIC LIBRARY SCIENCE, 2014-01-27)
    A fundamental goal of neuroscience is to understand how cognitive processes, such as operant conditioning, are performed by the brain. Typical and well studied examples of operant conditioning, in which the firing rates of individual cortical neurons in monkeys are increased using rewards, provide an opportunity for insight into this. Studies of reward-modulated spike-timing-dependent plasticity (RSTDP), and of other models such as R-max, have reproduced this learning behavior, but they have assumed that no unsupervised learning is present (i.e., no learning occurs without, or independent of, rewards). We show that these models cannot elicit firing rate reinforcement while exhibiting both reward learning and ongoing, stable unsupervised learning. To fix this issue, we propose a new RSTDP model of synaptic plasticity based upon the observed effects that dopamine has on long-term potentiation and depression (LTP and LTD). We show, both analytically and through simulations, that our new model can exhibit unsupervised learning and lead to firing rate reinforcement. This requires that the strengthening of LTP by the reward signal is greater than the strengthening of LTD and that the reinforced neuron exhibits irregular firing. We show the robustness of our findings to spike-timing correlations, to the synaptic weight dependence that is assumed, and to changes in the mean reward. We also consider our model in the differential reinforcement of two nearby neurons. Our model aligns more strongly with experimental studies than previous models and makes testable predictions for future experiments.
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    Feasibility of a Chronic, Minimally Invasive Endovascular Neural Interface
    Opie, NL ; Rind, GS ; John, SE ; Ronayne, SM ; Grayden, DB ; Burkitt, AN ; May, CN ; O'Brien, TJ ; Oxley, TJ ; Patton, J ; Barbieri, R ; Ji, J ; Jabbari, E ; Dokos, S ; Mukkamala, R ; Guiraud, D ; Jovanov, E ; Dhaher, Y ; Panescu, D ; Vangils, M ; Wheeler, B ; Dhawan, AP (IEEE, 2016)
    Development of a neural interface that can be implanted without risky, open brain surgery will increase the safety and viability of chronic neural recording arrays. We have developed a minimally invasive surgical procedure and an endovascular electrode-array that can be delivered to overlie the cortex through blood vessels. Here, we describe feasibility of the endovascular interface through electrode viability, recording potential and safety. Electrochemical impedance spectroscopy demonstrated that electrode impedance was stable over 91 days and low frequency phase could be used to infer electrode incorporation into the vessel wall. Baseline neural recording were used to identify the maximum bandwidth of the neural interface, which remained stable around 193 Hz for six months. Cross-sectional areas of the implanted vessels were non-destructively measured using the Australian Synchrotron. There was no case of occlusion observed in any of the implanted animals. This work demonstrates the feasibility of an endovascular neural interface to safely and efficaciously record neural information over a chronic time course.
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    A Possible Role for End-Stopped V1 Neurons in the Perception of Motion: A Computational Model
    Eskikand, PZ ; Kameneva, T ; Ibbotson, MR ; Burkitt, AN ; Grayden, DB ; Chacron, MJ (PUBLIC LIBRARY SCIENCE, 2016-10-14)
    We present a model of the early stages of processing in the visual cortex, in particular V1 and MT, to investigate the potential role of end-stopped V1 neurons in solving the aperture problem. A hierarchical network is used in which the incoming motion signals provided by complex V1 neurons and end-stopped V1 neurons proceed to MT neurons at the next stage. MT neurons are categorized into two types based on their function: integration and segmentation. The role of integration neurons is to propagate unambiguous motion signals arriving from those V1 neurons that emphasize object terminators (e.g. corners). Segmentation neurons detect the discontinuities in the input stimulus to control the activity of integration neurons. Although the activity of the complex V1 neurons at the terminators of the object accurately represents the direction of the motion, their level of activity is less than the activity of the neurons along the edges. Therefore, a model incorporating end-stopped neurons is essential to suppress ambiguous motion signals along the edges of the stimulus. It is shown that the unambiguous motion signals at terminators propagate over the rest of the object to achieve an accurate representation of motion.
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    Spike history neural response model
    Kameneva, T ; Abramian, M ; Zarelli, D ; Nesic, D ; Burkitt, AN ; Meffin, H ; Grayden, DB (SPRINGER, 2015-06)
    There is a potential for improved efficacy of neural stimulation if stimulation levels can be modified dynamically based on the responses of neural tissue in real time. A neural model is developed that describes the response of neurons to electrical stimulation and that is suitable for feedback control neuroprosthetic stimulation. Experimental data from NZ white rabbit retinae is used with a data-driven technique to model neural dynamics. The linear-nonlinear approach is adapted to incorporate spike history and to predict the neural response of ganglion cells to electrical stimulation. To validate the fitness of the model, the penalty term is calculated based on the time difference between each simulated spike and the closest spike in time in the experimentally recorded train. The proposed model is able to robustly predict experimentally observed spike trains.
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    Broadband Onset Inhibition Can Suppress Spectral Splatter in the Auditory Brainstem
    Spencer, MJ ; Nayagam, DAX ; Clarey, JC ; Paolini, AG ; Meffin, H ; Burkitt, AN ; Grayden, DB ; Chacron, MJ (PUBLIC LIBRARY SCIENCE, 2015-05-15)
    In vivo intracellular responses to auditory stimuli revealed that, in a particular population of cells of the ventral nucleus of the lateral lemniscus (VNLL) of rats, fast inhibition occurred before the first action potential. These experimental data were used to constrain a leaky integrate-and-fire (LIF) model of the neurons in this circuit. The post-synaptic potentials of the VNLL cell population were characterized using a method of triggered averaging. Analysis suggested that these inhibited VNLL cells produce action potentials in response to a particular magnitude of the rate of change of their membrane potential. The LIF model was modified to incorporate the VNLL cells' distinctive action potential production mechanism. The model was used to explore the response of the population of VNLL cells to simple speech-like sounds. These sounds consisted of a simple tone modulated by a saw tooth with exponential decays, similar to glottal pulses that are the repeated impulses seen in vocalizations. It was found that the harmonic component of the sound was enhanced in the VNLL cell population when compared to a population of auditory nerve fibers. This was because the broadband onset noise, also termed spectral splatter, was suppressed by the fast onset inhibition. This mechanism has the potential to greatly improve the clarity of the representation of the harmonic content of certain kinds of natural sounds.
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    Retinal ganglion cells electrophysiology: the effect of cell morphology on impulse waveform
    Maturana, MI ; Wong, R ; Cloherty, SL ; Ibbotson, MR ; Hadjinicolaou, AE ; Grayden, DB ; Burkitt, AN ; Meffin, H ; O'Brien, BJ ; Kameneva, T (IEEE, 2013)
    There are 16 morphologically defined classes of rats retinal ganglion cells (RGCs). Using computer simulation of a realistic anatomically correct A1 mouse RGC, we investigate the effect of the cell's morphology on its impulse waveform, using the first-, and second-order time derivatives as well as the phase plot features. Using whole cell patch clamp recordings, we recorded the impulse waveform for each of the rat RGCs types. While we found some clear differences in many features of the impulse waveforms for A2 and B2 cells compared to other cell classes, many cell types did not show clear differences.
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    First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis
    Ayton, LN ; Blamey, PJ ; Guymer, RH ; Luu, CD ; Nayagam, DAX ; Sinclair, NC ; Shivdasani, MN ; Yeoh, J ; McCombe, MF ; Briggs, RJ ; Opie, NL ; Villalobos, J ; Dimitrov, PN ; Varsamidis, M ; Petoe, MA ; McCarthy, CD ; Walker, JG ; Barnes, N ; Burkitt, AN ; Williams, CE ; Shepherd, RK ; Allen, PJ ; Mori, K (PUBLIC LIBRARY SCIENCE, 2014-12-18)
    UNLABELLED: Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. TRIAL REGISTRATION: Clinicaltrials.gov NCT01603576.