Doctor of Philosophy

dissertationThe goal of this work is to construct a simulation toolset for studying and improving neuroprosthetic devices for restoring neural functionality to patients with neural disorders or diseases. This involves the construction and validation of coupled electromagnetic-neural computational models of retina and hippocampus, compiling knowledge from a broad multidisciplinary background into a single computational platform, with features specific to implant electronics, bulk tissue, cellular and neural network behavior, and diseased tissue. The application of a retina prosthetic device for restoring partial vision to patients blinded by degenerative diseases was first considered. This began with the conceptualization of the retina model, translating features of a connectome, implant electronics, and medical images into a computational model that was "degenerated." It was then applied to the design of novel electrode geometries towards increasing the resolution of induced visual percept, and of stimulation waveform shapes for increasing control of induced neural activity in diseased retina. Throughout this process, features of the simulation toolset itself were modified to increase the precision of the results, leading to a novel method for computing effective bulk resistivity for use in such multiscale modeling. This simulation strategy was then extended to the application of a hippocampus prosthetic device, which has been proposed to restore and/or enhance memory in patients with memory disorders such as Alzheimer's disease or dementia. Using this multiscale modeling approach, we are able to provide recommendations for electrode geometry, placement, and stimulation magnitude for increased safety and efficacy in future experimental trials. In attempt to model neural activity in dense hippocampal tissue, a simulation platform for considering the effects the electrical activity of neural networks have on the extracellular electric field, and therefore have on their neighboring cells, was constructed, further increasing the predictive ability of the proposed methodology for modeling electrical stimulation of neural tissue

On the Modeling of Electrical Effects Experienced by Space Explorers During Extra Vehicular Activities: Intracorporal Currents, Resistances, and Electric Fields

Recent research has shown that space explorers engaged in Extra Vehicular Activities (EVAs) may be exposed, under certain conditions, to undesired electrical currents. This work focuses on determining whether these undesired induced electrical currents could be responsible for involuntary neuromuscular activity in the subjects, possibly caused by either large diameter peripheral nerve activation or reflex activity from cutaneous afferent stimulation. An efficient multiresolution variant of the admittance method along with a millimeter-resolution model of a male human body were used to calculate induced electric fields, resistance between contact electrodes used to simulate the potential exposure condition, and currents induced in the human body model. Results show that, under realistic exposure conditions using a 15V source, current density magnitudes and total current injected are well above previously reported startle reaction thresholds. This indicates that, under the considered conditions, the subjects could experience involuntary motor response

Admittance Method for Estimating Local Field Potentials Generated in a Multi-Scale Neuron Model of the Hippocampus

Significant progress has been made toward model-based prediction of neral tissue activation in response to extracellular electrical stimulation, but challenges remain in the accurate and efficient estimation of distributed local field potentials (LFP). Analytical methods of estimating electric fields are a first-order approximation that may be suitable for model validation, but they are computationally expensive and cannot accurately capture boundary conditions in heterogeneous tissue. While there are many appropriate numerical methods of solving electric fields in neural tissue models, there isn\u27t an established standard for mesh geometry nor a well-known rule for handling any mismatch in spatial resolution. Moreover, the challenge of misalignment between current sources and mesh nodes in a finite-element or resistor-network method volume conduction model needs to be further investigated. Therefore, using a previously published and validated multi-scale model of the hippocampus, the authors have formulated an algorithm for LFP estimation, and by extension, bidirectional communication between discretized and numerically solved volume conduction models and biologically detailed neural circuit models constructed in NEURON. Development of this algorithm required that we assess meshes of (i) unstructured tetrahedral and grid-based hexahedral geometries as well as (ii) differing approaches for managing the spatial misalignment of current sources and mesh nodes. The resulting algorithm is validated through the comparison of Admittance Method predicted evoked potentials with analytically estimated LFPs. Establishing this method is a critical step toward closed-loop integration of volume conductor and NEURON models that could lead to substantial improvement of the predictive power of multi-scale stimulation models of cortical tissue. These models may be used to deepen our understanding of hippocampal pathologies and the identification of efficacious electroceutical treatments

A ‘just and lasting solution’ to the Cyprus problem: In search of institutional viability

This paper examines the possible nature of a ‘just and lasting solution’ to the Cyprus Problem. Four factors are seen to affect the viability of a solution namely, the relative capacity of the Greek and Turkish Cypriot sides to impose costs in the event of either breaking off from inter-ethnic co-operation, the extent to which each party perceives the solution to be fair, the continuous influence of informal rules which may promote ethnic identification and finally, the judicial enforcement and legislative maintenance of the agreed solution. The discussion generates a number of insights into several aspects of the dispute including, security guarantees, territorial adjustments, the freedom of movement and establishment and the right of property, a federal versus a confederal solution and finally, the desirable nature of the constitution of a multi-ethnic Cyprus