Doctor of Philosophy, Case Western Reserve University, 2014, Physiology and Biophysics

Mesial temporal lobe epilepsy (MTLE) is the most common and medically refractory form of epilepsy. As an alternative to surgical resection, MTLE has been treated with vagal nerve stimulation and deep brain electrical stimulation (DBS) of gray matter with limited success. Stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency electrical stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goals of this study are: (i) To understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation, (ii) To develop and test a novel DBS paradigm for hippocampal seizure reduction, and (iii) To test the role of long-lasting hyperpolarization in mediating the anti-epileptic effects of LFS. The third objective is divided into two parts as follows: (a) Pharmacologically assess whether GABAB receptors are necessary for seizure reduction by LFS and (b) Pharmacologically assess whether the sAHP is necessary for seizure reduction by LFS. To achieve these aims, LFS is applied to the VHC as electrophysiological techniques are combined with signal processing to estimate several metrics of epilepsy. Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces seizures in bilateral hiipocampi during and after stimulation in an amplitude and frequency dependent manner. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Understanding the mechanisms of seizure reduction by LFS is important for minimizing side effects of this potential therapy and maximizing efficacy. This study shows dep (open full item for complete abstract)

Committee: Dominique Durand (Advisor); Corey Smith (Committee Chair); George Dubyak (Committee Member); Thomas Nosek (Committee Member); Christopher Ford (Committee Member); Ruth Siegel (Committee Member); Imad Najm (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Biophysics; Neurology; Neurosciences

PhD, University of Cincinnati, 2009, Arts and Sciences : Psychology

The classic receptive (temporal lobe)/generative (frontal lobe) dissociation of language function may be inadequate in characterizing language function in epilepsy. The relative impact of temporal versus frontal lobe epileptogenic foci on language function is also unknown. Individuals with mesial temporal lobe epilepsy (MTLE), have higher rates of psychopathology relative to the general and other chronically ill populations, as well as structural hippocampal abnormalities associated independently with the MTLE syndrome and the effects of high levels of emotional distress. Therefore, cognitive dysfunction may result from some combination of the intrinsic epileptogenic lesion or damage associated with chronic high levels of emotional distress, or both. The present study evaluted the diagnostic utility of the Boston Naming Test, phonemic paraphasic error production on the BNT, Controlled Oral Word Association Task, Animal Naming, and Token Test in terms of their ability to predict frontal lob epilepsy (FLE), left MTLE, or right MTLE focus, as well as the potentially moderating effects of perceived emotional distress. Seventy-seven individuals with MTLE (43 left and 34 right) and 30 individuals with FLE were included. Binary logistic regression models evaluated the predictive ability of each language measure to differentiate diagnostic group. Main effect and interaction terms for scales D and Pt on the MMPI-2 were added to each model to assess the possible moderating effects of perceived emotional distress. The results did not explicitly support a receptive/generative dichotomy, but rather a continuum of language function with some tasks more or less reliant on receptive and generative language components. Left MTLE and FLE patients performed equally poorly on all language measures, while right MTLE patient performance was largely unimpaired. Performance was moderated by perceived emotional distress; however, depression and anxiety were found to differentially modera (open full item for complete abstract)

Committee: Bruce Schefft PhD (Committee Chair); Steven Howe PhD (Committee Member); Michael Privitera MD (Committee Member); Christine Hovantiz PhD (Committee Member) Subjects: Psychology