Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Co-Chair: Shawn Hochman; Committee Co-Chair: Stephen P. DeWeerth; Committee Member: Lena Ting; Committee Member: Robert J. Butera; Committee Member: Robert Lee; Committee Member: Vivian K. Mushahwar. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph. D.)--Michigan State University. Electrical Engineering, 2008. / Title from PDF t.p. (Proquest, viewed on Aug. 17, 2009) Includes bibliographical references (p. 120-135). Also issued in print.

Thesis (M.S.)--State University of New York at Binghamton, Department of Psychology, 2008. / Includes bibliographical references.

Honors Project--Smith College, Northampton, Mass., 2010. / Includes bibliographical references (p. 56-59).

<p>Epidural cortical stimulation (ECS) is a developing therapy for many neurological disorders. However, the mechanisms by which ECS has its effects are unknown, and this lack of understanding has limited the development and optimization of this promising therapy. This dissertation investigates the effects of ECS on the neurons in the cortex and how these effects vary with electrode geometry and location as well as the electrical and geometrical properties of the anatomy.</p><p>The effects of ECS on cortical neurons were investigated using a three dimensional computational model of the human precentral gyrus and surrounding anatomy. An epidural electrode was placed above the gyrus, and the model was solved using the finite element method. The outputs of the model included distributions of electric potential, the second spatial derivative of potential (activating function), and current density. The distributions of electric potential were coupled to compartmental models of cortical neurons to quantify the effects of ECS on cortical neurons. A sensitivity analysis was performed to assess how thresholds and distributions of activating function were impacted by changes in the geometrical and electrical properties of the model. In vivo experiments of epidural electrical stimulation of cat motor cortex were performed to measure the effects of stimulation parameters and electrode location on thresholds for evoking motor responses.</p><p>During ECS, the region of cortex directly underneath the electrode was activated at the lowest thresholds, and neurons deep in the sulcus could not be directly activated without coactivation of neurons located on the crowns or lips of the gyri. The thresholds for excitation of cortical neurons depended on stimulation polarity as well as the orientation and position of the neurons with respect to the electrode. In addition, the patterns and spatial extent of activation were influenced by the geometry of the cortex and surrounding layers, the dimensions of the electrodes, and the positioning of the lead. In vivo thresholds for evoking motor responses were dependent on electrode location and stimulation polarity, and bipolar thresholds were often different from monopolar thresholds through the respective anode and cathode individually. The effects of stimulation polarity and electrode location on thresholds for evoking motor responses paralleled results of the computational model. Experimental evidence of indirect effects of ECS, mediated by synaptic interactions between neural elements, revealed an opportunity for further development of the computational model. The outcome of this dissertation is an improved understanding of the factors that influence the effects of ECS on cortical neurons, and this knowledge will help facilitate the rational implantation and programming of ECS systems.</p> / Dissertation

Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on Jan. 20, 2010. Major professor: Dr. Lynne Slivovsky. "Presented to the faculty of the College of Engineering, California Polytechnic State University." "In partial fulfillment of the requirements for the degree [of] Master of Science in Electrical Engineering." "July 2009." Includes bibliographical references (p. 102-104).

Willfully controlling the focus of an extracellular stimulus remains a significant challenge in the development of neural prosthetics and therapeutic devices. In part, this challenge is due to the vast set of complex interactions between the electric fields induced by the microelectrodes and the complex morphologies and dynamics of the neural tissue. Overcoming such issues to produce methodologies for targeted neural stimulation requires a system that is capable of (1) delivering precise, localized stimuli a function of the stimulating electrodes and (2) recording the locations and magnitudes of the resulting evoked responses a function of the cell geometry and membrane dynamics. In order to improve stimulus delivery, we developed microfabrication technologies that could specify the electrode geometry and electrical properties. Specifically, we developed a closed-loop electroplating strategy to monitor and control the morphology of surface coatings during deposition, and we implemented pulse-plating techniques as a means to produce robust, resilient microelectrodes that could withstand rigorous handling and harsh environments. In order to evaluate the responses evoked by these stimulating electrodes, we developed microscopy techniques and signal processing algorithms that could automatically identify and evaluate the electrical response of each individual neuron. Finally, by applying this simultaneous stimulation and optical recording system to the study of dissociated cortical cultures in multielectode arrays, we could evaluate the efficacy of excitatory and inhibitory waveforms. Although we found that the proximity of the electrode is a poor predictor of individual neural excitation thresholds, we have shown that it is possible to use inhibitory waveforms to globally reduce excitability in the vicinity of the electrode. Thus, the developed system was able to provide very high resolution insight into the complex set of interactions between the stimulating electrodes and populations of individual neurons.

Access to and subsequent control of spinal cord function are critical considerations for design of optimal therapeutic strategies for SCI patients. Electrical stimulation of the spinal cord is capable of activating behaviorally-relevant populations of neurons for recovery of function, and is therefore an attractive target for potential devices. A promising method for accessing these spinal circuits is through their axons, which are organized as longitudinal columns of white matter funiculi along the cord exterior. For this thesis, I hypothesized that these funiculi can be selectively recruited via electrodes appropriately placed on the surface of the spinal cord, for functional activation of relevant motor circuitry in a chronically-transected spinal cord. My tandem design goal was to fabricate and implement a conformable multi-electrode array (MEA) that would enable this selective stimulation. To accomplish this design goal, I participated in the design, fabrication, and electromechanical testing of a conformable MEA for surface stimulation of spinal tracts. I then assessed the fundamental capability of this MEA technology to stimulate white matter tracts in a precise, controlled, and functionally-relevant manner. This was accomplished via in vitro experiments that explored the ability of this MEA to locally activate axons via single- and dual-site surface stimulation. The results from these evaluation studies suggest that spinal-cord surface stimulation with this novel MEA technology can provide discrete, minimally-damaging activation of spinal systems via their white matter tracts. To test my hypothesis that surface stimulation can be used to recruit distinct populations in the spinal cord, I performed studies that stimulated lateral funiculi in both chronically-transected and intact in vitro spinal cords. Results from these studies reveal that selective surface stimulation of white matter tracts in the ventrolateral funiculus (VLF) elicit motor outputs not elicited in intact cords. In addition, I was able to demonstrate that the spinal systems activated by this surface stimulation involve synaptic components and are responsive to spatial, temporal, and pharmacologic facilitation. Corresponding labeling of the axonal tracts projecting through the T12 VLF indicate that, after chronic transection, the remaining spinal neurons whose axons travel through the VLF include those with cell bodies in both the intermediate region and dorsal horn. These electrophysiological results show that surface-stimulating technologies used to control motor function after injury should include focal activation of interneuronal systems with axons in the ventrolateral funiculus. As a whole, these studies provide essential starting points for further use of conformable MEAs to effectively activate and control spinal cord function from the surface of the spinal cord.

In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomesare modest, infrared neural stimulation (INS) was applied to the cochlear nucleus in a ratanimal model. Pulsed INS, delivered to the surface of the cochlear nucleus via an opticalfibre, evoked auditory brainstem responses (ABR) and generated broad neural activation inthe inferior Colliculus (IC). Varying the parameters of the laser stimulation revealed laserpeak power to be the dominating parameter for both ABR and IC responses. Strongestresponses were recorded when the fibre was placed at lateral positions on the cochlearnucleus, close to the temporal bone. After deafening by auditory nerve section, ABR andIC responses to INS disappeared, consistent with a reported "optophonic" effect, a laser-inducedacoustic artifact. Thus, for deaf individuals who use the auditory brainstemimplant, INS alone does not appear promising as a new approach.

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