Abstracts

Rationale: Epileptiform discharges are potentiated by sleep in several epilepsy syndromes, but the cause of this phenomenon is not well understood. The thalamus is an important brain nucleus with extensive cortical connections and intimately involved in regulation of sleep physiology. Previous work has found that early thalamic injury may predispose patients to sleep-potentiated spikes (Ferna´ndez et al. 2012, Leal et al. 2018), but the mechanism of this relationship is not known. Benign childhood epilepsy with centrotemporal spikes (BECTS) is a common pediatric epilepsy syndrome characterized by stereotyped sleep-potentiated spike activity present independently in bilateral primary sensorimotor cortices. As BECTS presents during a period of dramatic white matter development, we hypothesized that alterations in thalamocortical connectivity to the primary sensorimotor seizure onset zone (SOZ) would be present in children with BECTS and correlate with spike burden during sleep. Methods: Twenty-three children with BECTS and 19 healthy controls were recruited for this study. Four subjects returned for longitudinal scans. Subjects underwent 3 Tesla diffusion-weighted magnetic resonance imaging (2mm x 2mm x 2mm) with 64 gradient directions (b-value=2000) and 72 electrode sleep-deprived electroencephalographic (EEG) recordings. EEG spikes were manually marked during all available non-REM sleep epochs and summed over the time interval (range 0.002-0.625 spikes per second). Seed and target regions of interest (ROIs) were created within each hemisphere using the Desikan-Killiany atlas, with the thalamus set as a seed ROI, and SOZ cortex and non-SOZ (NSOZ) cortex as target ROIs. To infer the structural connectivity between thalamic and cortical ROI pairs, probabilistic tractography was executed using Probtrackx2 (Behrens et al. 2003) with 500 streamlines per seed voxel, 0.5 millimeter steps, and a curvature threshold of 0.2. All streamlines reaching the target ROI were summed and normalized by seed voxel count. Results for BECTS and healthy controls were plotted by age. The slope of thalamocortical connectivity versus age was computed for each group and compared between groups using nonparametric bootstrap analysis. We also compared thalamocortical connectivity with spike burden using a linear regression model, controlling for age. Results: We found a significant difference in the developmental trajectory of thalamocortical connectivity to the SOZ in BECTS cases compared to healthy controls (p=0.014), where the increase in connectivity with age observed in healthy controls was not present in BECTS children. These results did not extend to NSOZ thalamocortical connections (p=0.192). Longitudinal results support these observations, where all BECTS cases who underwent repeat imaging (n=4) showed a decrease in thalamocortical connectivity to the SOZ over the follow-up period. No relationship was found between thalamocortical connectivity and spike burden (p=0.840). Conclusions: These results suggest that subtle aberrations in white matter development are present in BECTS. Thalamocortical connectivity does not appear to directly mediate sleep spike potentiation in BECTS. Funding: NINDS K23-NS092923