The work of this thesis was to develop and use such a computational model to offer insight into the working mechanisms of cochlear implant stimulation and to enable virtual experiments that would... Show moreThe work of this thesis was to develop and use such a computational model to offer insight into the working mechanisms of cochlear implant stimulation and to enable virtual experiments that would be unfeasible or outright impossible in real life. The model that was used for this thesis was not built from scratch but was an updated and expanded version of the one developed at Leiden University Medical Centre by Johan H.M. Frijns and Jeroen J. Briaire. In essence, this thesis forms a continuation of their PhD work. The general goals of each of the modelling studies presented in this thesis were:(I) To improve the accuracy of the Leiden computational cochlear implant model to gain a better understanding of cochlear implant-induced hearing.(II) Where possible, validate the model using available data from electrophysiological or psychophysical experiments.(III) To use the model to offer predictions that may help to improve the function or design of cochlear implants in the future. Show less
The main aim of this computational modelling study was to test the validity of the hypothesis that sensitivity to the polarity of cochlear implant stimulation can be interpreted as a measure of... Show moreThe main aim of this computational modelling study was to test the validity of the hypothesis that sensitivity to the polarity of cochlear implant stimulation can be interpreted as a measure of neural health. For this purpose, the effects of stimulus polarity on neural excitation patterns were investigated in a volume conduction model of the implanted human cochlea, which was coupled with a deterministic active nerve fibre model based on characteristics of human auditory neurons. The nerve fibres were modelled in three stages of neural degeneration: intact, with shortened peripheral terminal nodes and with complete loss of the peripheral processes. The model simulated neural responses to monophasic, biphasic, triphasic and pseudomonophasic pulses of both polarities. Polarity sensitivity was quantified as the so-called polarity effect (PE), which is defined as the dB difference between cathodic and anodic thresholds. Results showed that anodic pulses mostly excited the auditory neurons in their central axons, while cathodic stimuli generally excited neurons in their peripheral processes or near their cell bodies. As a consequence, cathodic thresholds were more affected by neural degeneration than anodic thresholds. Neural degeneration did not have a consistent effect on the modelled PE values, though there were notable effects of electrode contact insertion angle and distance from the modiolus. Furthermore, determining PE values using charge-balanced multiphasic pulses as approximations of monophasic stimuli produced different results than those obtained with true monophasic pulses, at a degree that depended on the specific pulse shape; in general, pulses with lower secondary phase amplitudes showed polarity sensitivities closer to those obtained with true monophasic pulses. The main conclusion of this study is that polarity sensitivity is not a reliable indicator of neural health; neural degeneration affects simulated polarity sensitivity, but its effect is not consistently related to the degree of degeneration. Polarity sensitivity is not simply a product of the state of the neurons, but also depends on spatial factors.(c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
This thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.Regarding metabolism, we present ZebraGEM 2.0, an improved whole-genome... Show moreThis thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.Regarding metabolism, we present ZebraGEM 2.0, an improved whole-genome scale metabolic reconstruction for zebrafish, that we used to study zebrafish metabolism upon infection with Mycobacterium marinum integrating gene expression data from control and infected zebrafish larvae. The chapters focusing on cell motility in response to the environment, revolve around the question of how the environmental inputs of cell-matrix interactions, cell-sized obstacles and cell-signalling upon wounding shape and guide cell motility. Show less
With commonly used monopolar or __single electrode stimulation__ (SES) in cochlear implants the perceived pitch depends on the place in the cochlea of the stimulated contact. When two contacts are... Show moreWith commonly used monopolar or __single electrode stimulation__ (SES) in cochlear implants the perceived pitch depends on the place in the cochlea of the stimulated contact. When two contacts are stimulated simultaneously, __dual electrode stimulation__(DES), intermediate pitches can be elicited. The place and precise pitch can be adjusted by varying the current ratio between these two contacts. In this thesis the mechanism of DES is investigated psychophysically, electrophysiologically and in a computational model of the cochlea. It was concluded that DES and SES are indistinguishable in terms of spread of excitation and sequential channel interaction, while with DES the pitch depends linearly on the current ratio. On adjacent contacts, DES turned out to be effective for the entire dynamic range without the need for any current correction to equalize loudness between pitches. DES is also feasible on non-adjacent contacts (__spanning__) up till 4.4 mm, but with increasing distance between the contacts, such a current correction becomes mandatory, while also the number of discriminable pitches decreases. Finally, spanning was implemented in a speech coding strategy and tested in a take-home trial, which demonstrated that even with two groups of three adjacent defective contacts, speech perception and sound quality were retained. Show less
