Date of Award

Summer 8-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Levi B Good

Abstract

Epilepsy is a common and disabling neurological condition affecting 1-2% of the world’s population. Individuals suffering from epilepsy are prone to cognitive dysfunctions with detrimental effects in neural processing and memory resulting in decreases in quality of life. An evaluation of inherent neural processes is valuable information to diagnose and clinically assess cognitive function, which could significantly improve the treatment possibilities and thereby the quality of life for epilepsy patients.

An evaluation of cognitive functions during epileptogenesis was performed by experiments using auditory event related potentials (ERP) in rats before and after induction of status epilepticus (SE) using the Lithium-Pilocarpine model (LP) of epilepsy. The aim of this study was to assess changes in neural system function during epileptogenesis by evaluating inherent responses to auditory stimuli in three ERP tasks at different time periods: before SE (control state), one week-, one month- and two months- after SE (epileptic state). 1. Habituation- (a.) evaluate the ability to habituate to repeated auditory stimuli using the N70 peak response, (b.) examine the time-frequency response through inter-trial coherence (ITC) and event-related spectral perturbation (ERSP); 2. Chirp- evaluate the auditory steady state responses through ITC; and, 3. Mismatch-Negativity (MMN)- evaluate associative memory through ERP responses to regular or odd tones.

Habituation tasks showed increased N70 peak magnitude during epileptogenesis from 1-week, 1-month, and 2-months after SE using repeated measures analysis of variance (rANOVA) with significant differences before and after SE (p<0.05, 1-week, 2-months). ITC showed significant differences between groups during habituation from 0.5-20 Hz and ERSP from 60-100 Hz and 0.5-15 Hz, with baseline corrected ERSP revealing differences from 1-30 Hz. The habituation results indicate a diminished ability to properly habituate to repeated stimuli with abnormal neuronal firing in the epileptic state compared to the non-epileptic control state linking a possible mechanism with imbalances in neuronal inhibition and excitation during epileptogenesis. Chirp response ITC showed increased synchronous activity in high gamma band (>40 Hz) during epileptogenesis indicating the neuronal response in epileptic groups are phase locked to the chirp stimuli at a higher incidence than controls. Epileptic MMN ERP responses for odd and regular tones exhibited a decrease in the response curves from 250-350ms post-stimulus indicating a loss of ability to distinguish tones and difficulties with their associative memory during epileptogenesis.

Our results indicate that a proper EEG-based analysis of auditory ERPs are useful in evaluating neural systems during epileptogenesis showing clear imbalances in excitatory: inhibitory function, as well as an indication that associative memory is detrimentally affected. The ERP methods employed may help in the diagnosis of the epileptic patients with cognitive disabilities as their epilepsy progresses, as it is simple, non-invasive and cost effective.

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