Biomedical Engineering - Research Publications
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ItemNo Preview AvailableAmbient air pollution and epileptic seizures: A panel study in AustraliaChen, Z ; Yu, W ; Xu, R ; Karoly, PJ ; Maturana, M ; Payne, DE ; Li, L ; Nurse, ES ; Freestone, DR ; Li, S ; Burkitt, AN ; Cook, MJ ; Guo, Y ; Grayden, DB (WILEY, 2022-04-26)OBJECTIVE: Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures. METHODS: This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista data set, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010-2012. In the seizure diary data set, 3419 self-reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018-2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO2 ), ozone (O3 ), particulate matter ≤10 μm in diameter (PM10 ), and sulfur dioxide (SO2 ) were retrieved from the Environment Protection Authority (EPA) based on participants' postcodes. A patient-time-stratified case-crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures. RESULTS: A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01-1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), whereas no significant associations were found for the other four air pollutants in the whole study population. Female participants had a significantly increased risk of seizures when exposed to elevated CO and NO2 , with RRs of 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.01-1.16), respectively. In addition, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12-1.28). SIGNIFICANCE: Daily exposure to elevated CO concentrations may be associated with an increased risk of epileptic seizures, especially for subclinical seizures.
ItemElectrical probing of cortical excitability in patients with epilepsyFreestone, DR ; Kuhlmann, L ; Grayden, DB ; Burkitt, AN ; Lai, A ; Nelson, TS ; Vogrin, S ; Murphy, M ; D'Souza, W ; Badawy, R ; Nesic, D ; Cook, MJ (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011-12-01)Standard methods for seizure prediction involve passive monitoring of intracranial electroencephalography (iEEG) in order to track the 'state' of the brain. This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus. Electrical probing enables feature extraction in a more robust and controlled manner compared to passively tracking features of iEEG signals. The probing stimuli consist of 100 bi-phasic pulses, delivered every 10 min. Features representing neural excitability are estimated from the iEEG responses to the stimuli. These features include the amplitude of the electrically evoked potential, the mean phase variance (univariate), and the phase-locking value (bivariate). In one patient, it is shown how the features vary over time in relation to the sleep-wake cycle and an epileptic seizure. For a second patient, it is demonstrated how the features vary with the rate of interictal discharges. In addition, the spatial pattern of increases and decreases in phase synchrony is explored when comparing periods of low and high interictal discharge rates, or sleep and awake states. The results demonstrate a proof-of-principle for the method to be applied in a seizure anticipation framework. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.
ItemA comparison of open-loop and closed-loop stimulation strategies to control excitation of retinal ganglion cellsKameneva, 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.
ItemNeural activity shaping utilizing a partitioned target patternSpencer, MJ ; Kameneva, T ; Grayden, DB ; Burkitt, AN ; Meffin, H (IOP PUBLISHING LTD, 2021-08-01)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.
ItemSeizure likelihood varies with day-to-day variations in sleep duration in patients with refractory focal epilepsy: A longitudinal electroencephalography investigationDell, KL ; Payne, DE ; Kremen, V ; Maturana, MI ; Gerla, V ; Nejedly, P ; Worrell, GA ; Lenka, L ; Mivalt, F ; Boston, RC ; Brinkmann, BH ; D'Souza, W ; Burkitt, AN ; Grayden, DB ; Kuhlmann, L ; Freestone, DR ; Cook, MJ (ELSEVIER, 2021-07-27)BACKGROUND: While the effects of prolonged sleep deprivation (≥24 h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management. METHODS: To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories. FINDINGS: Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 h, lowered the odds of seizure by 27% in the following 48 h. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced rapid eye movement sleep. INTERPRETATION: Our results suggest that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 h, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.
ItemLearning receptive field properties of complex cells in V1Lian, Y ; Almasi, A ; Grayden, DB ; Kameneva, T ; Burkitt, AN ; Meffin, H ; Einhäuser, W (PUBLIC LIBRARY SCIENCE, 2021-03-01)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.
ItemThe effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation resultsMaturana, MI ; Kameneva, T ; Burkitt, AN ; Meffin, H ; Grayden, DB (SPRINGER, 2014-04-01)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.
ItemCoexistence of Reward and Unsupervised Learning During the Operant Conditioning of Neural Firing RatesKerr, 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.
ItemAn investigation of dentritic delay in octopus cells of the mammalian cochlear nucleusSpencer, MJ ; Grayden, DB ; Bruce, IC ; Meffin, H ; Burkitt, AN (FRONTIERS RES FOUND, 2012-10-22)Octopus cells, located in the mammalian auditory brainstem, receive their excitatory synaptic input exclusively from auditory nerve fibers (ANFs). They respond with accurately timed spikes but are broadly tuned for sound frequency. Since the representation of information in the auditory nerve is well understood, it is possible to pose a number of questions about the relationship between the intrinsic electrophysiology, dendritic morphology, synaptic connectivity, and the ultimate functional role of octopus cells in the brainstem. This study employed a multi-compartmental Hodgkin-Huxley model to determine whether dendritic delay in octopus cells improves synaptic input coincidence detection in octopus cells by compensating for the cochlear traveling wave delay. The propagation time of post-synaptic potentials from synapse to soma was investigated. We found that the total dendritic delay was approximately 0.275 ms. It was observed that low-threshold potassium channels in the dendrites reduce the amplitude dependence of the dendritic delay of post-synaptic potentials. As our hypothesis predicted, the model was most sensitive to acoustic onset events, such as the glottal pulses in speech when the synaptic inputs were arranged such that the model's dendritic delay compensated for the cochlear traveling wave delay across the ANFs. The range of sound frequency input from ANFs was also investigated. The results suggested that input to octopus cells is dominated by high frequency ANFs.
ItemAdaptive Surround Modulation of MT Neurons: A Computational ModelZarei Eskikand, P ; Kameneva, T ; Burkitt, AN ; Grayden, DB ; Ibbotson, MR (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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