Abstracts

Rationale: The current study investigated brain networks during the early period of epileptogenesis using EEG and fMRI modalities to assess coupling between local and distal high frequency oscillation (HFO, 100-500Hz)-generating sites. Methods: Sixteen Sprague-Dawley rats were injected with kainic acid in the left CA3 area to induce status epilepticus (SE) and an equal number of rats served as the control group. One week before and 2 weeks after SE 10 minutes of BOLD data were acquired using a single-shot, gradient-echo, echo-planar, fMRI sequence (TR/TE=2000, 35ms with voxel sizes of 0.27×0.27×0.75mm) from rats under a bolus of medetomidine sedation (0.5 mL / 0.1mg/kg). We performed an independent component analysis in a separate cohort of 30 naive rats that were part of previous study to identify the resting-state networks (RSNs), and to guide the selection of regions-of-interest (ROIs) for electrode implantation in the current study. Here a total 16 bilateral ROIs representing the key structures of RSNs were selected. Two weeks after SE and the second fMRI depth electrodes were implanted in the ROIs that included left/right Prelimbic cortex (PrL), left/right Anterior Cingular cortex (ACg), left/right Retrosplenial cortex (RSC) left/right Primary/Secondary Motor cortex (M1/M2), left/right Thalamus (Thal), and left/right Dorsal/Ventral Hippocampus (DHip/VHip). Wide-band electrical activity was recorded continuously for 8 weeks. Twelve rats that later develop spontaneous epilepsy (E+) and 16 control rats were selected for a combinatorial analysis of fMRI and EEG data. Results: With respect to control rats our results found in E+ rats, (1) an increase of the local network connectivity and decreased of the distal network connectivity; (2) pairs of ROIs with increased BOLD functional connectivity (FC) were associated with stronger EEG coupling in EEG broadband (70-170Hz) and increased synchrony of multiunit discharges; and (3) HFO-HFO coupling increased in ROIs that had increased BOLD-FC and EEG-FC. These results suggest after an epileptogenic injury regional network dysregulation could produce local areas containing abnormal FC and hyperexcitability that support the development of epilepsy. We also found that the increased BOLD-FC corresponded with increased of appearance of pathological HFOs, increase of HFO-HFO couplings, and synchrony of EEG spikes. Conclusions: This study indicated the formation of PIN clusters during epileptogenesis were associated with the alteration of large-scale brain networks been captured by non-invasive method. Funding: R01-NS065877, R01-NS033310, R01-NS106957, and U54-NS100064