Rationale: Loss of consciousness (LOC), a hallmark of many epileptic seizures, is associated with life-threatening repercussions for the patients. It was suggested that LOC during complex partial seizures (CPS) is associated with thalamo-cortical sleep-like activities, while during generalized tonic-clonic seizures (GTC) it may relate to hypersynchronous cortical activity. Here we wished to explicitly test this hypothesis by quantifying differences in synchrony of markers of cortical recruitment and slow wave activity (SWA) patterns between GTC and CPS. Methods: We compared iEEG recordings from 42 epileptic patients, including 50 GTC and 129 CPS. We analyzed ictal iEEG activity in the seizure onset zone (SOZ) and in frontal, temporal, parietal, occipital and limbic regions >2 cm from the SOZ. To compare the extent of ictal recruitment between CPS and GTC, we compared their values of ictal high gamma power (80 - 150 Hz) phase-locked to lower frequencies (phased-locked high gamma, PLHG) in the different regions of interest. In both seizure types, we also quantified the number of channels that passed the Energy Ratio (ER) between high and low frequencies used to compute the Epileptogenicity Index. To compare differences in ictal synchrony during CPS vs. GTC, we then quantified differences in the proportion of channels that show more than 1 sec difference in timing for crossing the ER threshold. Additionally, we quantified differences in asynchrony for the timing of peak SWA power and of maximum amplitude of individually detected slow waves (SWs, using 30s sliding window, 1s step) across groups of channels during CPS vs. GTC. Results: During both GTC and CPS compared to baseline, we observed widespread increases in markers of ictal cortical recruitment. However, PLHG was significantly higher during GTC compared to CPS (especially after behavioral generalization). Additionally, more channels passed the ER threshold during GTC compared to CPS (73% vs. 51%, p< 0.001). Overall, the channels that least frequently passed ER during CPS were located in the parietal lobe (36% vs. 45-59%, p< 0.001 in comparison to the other lobes) and, during GTC, in the limbic network (65% vs 71-82%, p< 0.01 in comparison to the other lobes). Paradoxically, ictal recruitment was not only stronger, but was also more asynchronous during GTC as compared to CPS (with a higher proportion of channels crossing ER threshold more than 1s apart: 23% vs. 12%, p< 0.001). Peaks in SWA power and amplitudes of the SW also tended to be more asynchronous during GTC compared CPS (46% vs. 35%, p=0.015). Conclusions: Taken together, our results suggest more asynchrony in ictal dynamics (both for ictal recruitment and slow wave activity) during GTC compared to CPS. These findings challenge the hypothesis that LOC during GTC is a consequence of neuronal hypersynchrony. Increased asynchrony in ictal recruitment patterns may also favor the development of multiple intracranial foci in patients with frequent GTC and account for their more negative prognostic consequences. Funding: Please list any funding that was received in support of this abstract.: Tiny Blue Dot Foundation and Lily’s Fund for Epilepsy Research Grace Grant
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