Abstracts

Rationale: Rationale: Infantile spasms (IS) is an epileptic encephalopathy that is characterized by seizures called epileptic spasms. Although the electroencephalogram (EEG) of IS subjects is often disorganized with multifocal interictal spikes, this activity is characterized by strong, stable functional connectivity networks (FCNs) [1]. Here we investigate the impact of interictal spikes in IS EEG on the strength and structure of FCNs. Methods: Methods: We analyzed the FCNs in interictal sleep EEG in eight IS subjects and one subject with generalized focal epilepsy by computing the cross-correlation between electrode pairs in one-second epochs. For each subject, we generated three connectivity networks by selecting different subsets of epochs based on the occurrence of interictal spikes: (1) all epochs, (2) epochs containing focal spikes, and (3) epochs without spikes. We then compared connectivity strength and network structure across subjects for all three connectivity networks. For comparison, we analyzed the FCNs generated in sleep EEG for eight normal control subjects. We measured the changes in connectivity strength and network structure due to the addition of simulated, physiologically realistic, interictal spike waveforms. Results: Results: For subjects with IS and generalized epilepsy, we found that FCNs for epochs containing interictal spikes had the highest connectivity strength, followed by FCNs generated using all epochs, followed by FCNs without any interictal spikes. These differences were significant in 24 out of 27 comparisons. (Wilcoxon sign-rank test, n=27, Benjamini-Hochberg corrected, pFDR < 0.0374) (Table 1). In contrast, the inclusion of simulated interictal spike waveforms in control subject data did not significantly increase the connection strength. For both IS subjects and control subjects, we found that the presence of interictal spike waveforms did not change the connectivity structure. Two-dimensional correlation analysis between all three connectivity matrices of IS and epilepsy subjects revealed a significantly higher correlation coefficient for within-subject comparisons than between subjects (Wilcoxon rank-sum test, n=27, p<0.05), indicating that the patient-specific FCN structure was unaltered by the occurrence of interictal spikes. Similarly, we found that for control EEG, connectivity matrices with simulated interictal spikes had a significantly higher correlation coefficient within controls than across controls (Wilcoxon rank-sum test, n= 27, Bonferroni corrected, pFDR < 0.00185). Conclusions: Conclusions: Here, we evaluated the FCNs derived from sleep EEG and compared networks during focal interictal spikes to networks derived from epochs without any interictal spikes. In normal subjects with simulated spikes, we found that the presence of the spike waveform does not affect an individual’s core network structure or increase connectivity strength. In IS subjects, we found an increase in connectivity strength during interictal spikes, suggestive of an underlying pathological neural mechanism and supporting the hypothesis of subcortical driving in IS. Moreover, our simulations using healthy subjects suggest that this increase in strength is not an artifact generated purely by the presence of the spike waveform. Funding: Children’s Hospital of Orange Country (CHOC) PSF Tithe GrantICTS CHOC-UC Irvine Collaborative Pilot Grant