Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

Brian Litt

Abstract

In one-third of epilepsy patients, antiepileptic drugs do not effectively control seizures, leaving resective surgery as the primary treatment option. In the absence of discrete focal lesions, long-term outcome after surgery is modest and often associated with side effects. In many cases, surgery cannot be performed due to the lack of a discrete region generating seizures. For these reasons, new therapeutic technologies have been developed to treat drug-resistant epilepsy with electrical stimulation. These devices are promising, but the efficacy of first-generation implants has been limited. The work in this thesis aims to advance current approaches to seizure monitoring and control by developing better hardware and building the foundational knowledge behind the cortical dynamics underlying seizure generation, propagation and neural stimulation.

In this thesis, I first develop new technologies that sample local field potentials on the cortical surface with high spatial and temporal resolutions. These devices capture complex spatiotemporal patterns of epileptiform activity that are not detected on current clinical electrodes. By adding stimulation functionalities to these arrays, we position them as an ideal candidate for responsive, therapeutic neurostimulation. Next, I explore the effect of direct electrical stimulation in the cortex by recording responses with high spatial resolution on the surface and within the cortical laminae. The findings detail the capabilities and limitations of electrical stimulation as a means of modulating seizures. Finally, I use the same three-dimensional recording paradigm in feline neocortex to investigate the genesis and propagation of epileptiform activity in an isolated, chemically-induced epilepsy model. These experiments demonstrate that important circuit elements involved in seizure propagation are found deeper in the cortex and are not reflected in surface recordings. My investigations also present potential stimulation strategies to more effectively disrupt the spread of seizures in the neocortex. It is my hope that the results of this work will inform future technologies to better detect and prevent seizures, ultimately improving the lives of drug-resistant epilepsy patients through the next generation of implantable devices.

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