FMRI of brain activation in a genetic rat model of absence seizures

Abstract

Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions.

Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level-dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images.

Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area.

Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure.

FIG. 1

Representative EEG recording collected during functional magnetic resonance imaging (fMRI). Nonmagnetic epidural electrodes were placed in the frontal and parietal cortices to monitor seizure activity during the imaging session. Normal, awake EEG was present during baseline imaging. Imaging was triggered after the formation of epileptiform activity similar to that shown during the seizure period. Artifact due to image acquisition can be seen with a delay of ~2 s after seizure activity. RF, right frontal cortex; RP, right parietal cortex; LF, left frontal cortex; LP, left parietal cortex.

FIG. 2

Activation maps of blood-oxygen-level–dependent (BOLD) signal responses during spontaneous spike-and-wave discharges. Colored pixels, the statistically significant (p < 0.05) pixels determined by t test analysis (for a single seizure) and overlaid onto the corresponding anatomy. Three consecutive slices through the brain are shown for an individual rat. The top row shows the regions of interest used for analysis. MD, mediodorsal thalamic nuclei; nRT, nucleus reticularis thalami; Po, posterior thalamic nuclear group; PtA, parietal association cortex; S1, sensory cortex; Te, temporal cortex; VPM/VPL, ventral posteromedial/posterolateral thalamic nucleus.

FIG. 3

Change in blood-oxygen-level–dependent (BOLD) signal intensity for each region of interest (ROI). The BOLD signal intensity change during spike–wave discharges (SWDs) is shown for ROIs in the cortex and thalamus (mean ± SEM, n=34 seizures). All ROIs are bilateral structures, so the signal changes from each hemisphere were combined. BOLD signal was averaged for each seizure over the entire 30-s acquisition. MD, mediodorsal thalamic nuclei; nRT, nucleus reticularis thalami; Po, posterior thalamic nuclear group; PtA, parietal association cortex; S1, sensory cortex; Te, temporal cortex; VPM/VPL, ventral posteromedial/posterolateral thalamic nucleus.

FIG. 4

Change in blood-oxygen-level–dependent (BOLD) signal intensity over time for each region of interest (ROI) in the thalamus. All thalamic ROIs showed significant BOLD signal changes from baseline. All ROIs are bilateral structures, so the signal intensities from each hemisphere were combined. These plots were created by averaging the value for all seizures at each time point. Each image acquisition was 2 s. BOLD signal changes are shown for each baseline period, collected at different points throughout the imaging session. MD, mediodorsal thalamic nuclei; nRT, nucleus reticularis thalami; Po, posterior thalamic nuclear group; VPM/VPL, ventral posteromedial/posterolateral thalamic nucleus.

FIG. 5

Change in blood-oxygen-level–dependent (BOLD) signal intensity over time for each region of interest (ROI) in the cortex. All cortical ROIs showed significant BOLD signal changes from baseline. All ROIs are bilateral structures, so the signal intensities from each hemisphere were combined. These plots were created by averaging the value for all seizures at each time point. Each image acquisition was 2 s. BOLD signal changes are shown for each baseline period, collected at different points throughout the imaging session. PtA, parietal association cortex; S1, sensory cortex; Te, temporal cortex.