From electrical signals to biological processes: unveiling the complexity of electroencephalographic epileptiform spikes across sleep-wake states

This thesis introduces a novel investigation into the morphological characteristics of epileptiform spikes across various sleep-wake states. A gold-standard database of spikes was created, offering insights into their variations across wakefulness, non-rapid-eye-movement (NREM) sleep stages 1-3, and particularly rapid-eye-movement (REM) sleep, and hypothesizing on the dynamics regulating its suppressive ability towards spikes. The study employed lab-developed software to categorize sleep states and validate spikes using data from 7 epilepsy monitoring unit patients. A computational pipeline was developed to assess nine morphological spike features throughout Laplacian, Referential, and Raw montages. Due to non-normal data distribution, statistical analysis was performed using the Kruskal-Wallis test, followed by Dunn's post-hoc testing and Bonferroni correction. Results revealed that the spike features of REM sleep are significantly different from those of other sleep-wake states. In particular, spikes during REM sleep had the shallowest ascending and descending slopes by nearly 50% of the other states, which were nearly symmetrical, blunter peaks with roughly twice the angle of other states and exhibited lower peak amplitudes less than 50% of the voltage of other states. Wakefulness was the most different state concerning duration while being, on average, 15% shorter. Finally, the spike area during REM was roughly twice as small as all other states. This study shows significant spike feature differences throughout sleep-wake states, with REM drastically different in most features. The driving factors for changes in spike morphology throughout the sleep-wake states are unknown. However, this thesis explores the effects of ionic, neurotransmitter, astrocytic and network dynamic processes to help shed light on these changes. Notably, this thesis provides glimpses into the roles of astrocytic involvement, orexinergic systems, and network dynamics as potential contributors to the observed morphological differences ...