Abstracts

Rationale: Impaired conscious awareness greatly affects morbidity, mortality and quality of life for people with epilepsy, 30-40% of whom remain refractory to medical therapy. The mechanism of ictal loss of consciousness remains unclear. Limbic seizures have been shown in human and animal data to spread to arousal circuitry to result in a ‘network inhibition’ phenomenon resulting cortical dysfunction. However prior animal model studies have not yet related physiological network changes to behavioral responsiveness during or following seizures.

Methods: Adult female rats were implanted with lateral orbitofrontal and dorsal hippocampal electrodes. Animals were food restricted to 85% body weight and trained to respond to a 2-second 100 Hz clicking sound with a lick response into a metal spout affixed to a photobeam lickometer. Focal-onset limbic seizures were induced while rats were performing an operant conditioned behavioral task requiring response to an auditory stimulus to quantify how and when impairment of behavioral response occurs. Correct responses were rewarded with sucrose. Cortical and hippocampal electrophysiology measured by local field potential recordings was analyzed for changes in low and high frequency power in relation to behavioral responsiveness during seizures.

Results: Ictal (p< 0.0001) and postictal (p=0.0015) responsiveness to auditory stimulus showed variable impairment. In comparing correct and incorrect responses, cortical and hippocampal electrophysiology revealed that ictal (p=0.002) and postictal (p=0.009) frontal cortical low-frequency 3-6 Hz power was associated with poor behavioral performance. Hippocampal signal showed increased power over a wide frequency range during seizures and suppression post-ictally, neither of which were related to behavioral impairment.