Abstracts

Rationale: Childhood absence epilepsy (CAE) is characterized by EEG recordings of generalized, bilaterally synchronous 3 - 4 Hz spike and wave discharges (SWD) concurrent with behavioral arrest and loss of awareness. Recent EEG/fMRI studies in humans and in rats support a model in which SWDs arise from specific cortical foci, rather than occurring as a generalized phenomenon. Here we used magnetoencephalography (MEG) to identify the specific cortical regions active prior to and during absence seizures. Methods: Using simultaneous MEG and EEG measurements, we recorded absence seizures at 600 Hz from one 5 y/o and one 14 y/o female subject, and two 7 y/o male subjects, all of whom were recently diagnosed with CAE. Recordings were performed before treatment. Spontaneous SWDs were recorded during 0.5 - 2 hr period of data capture. Spectrograms and synthetic aperture magnetometry (SAM) were used to quantify preictal and ictal activity and their corresponding brain loci. SAM was conducted from 0.5 to 50 Hz in 500 ms increments starting 2 s prior to the seizure onset and ending 3 s after the seizure onset. The corresponding activation maps were coregistered with each subject s structural MRI. Results: Spectrograms revealed broad increases in ictal power over baseline conditions in the MEG sensors from 0-50 Hz with the onset of the first SWD spike, with the greatest power evident in frontal sensors. Up to 2 s prior to the onset of the seizure, SAM revealed significant activations (defined as activity different from baseline with all p s < 0.05) in the inferior frontal gyrus (3 of 4 subjects), middle (3 of 4) and superior (3 of 4) temporal gyri, and precentral gyrus (3 of 4). At the start of the seizure, all subjects exhibited strong activity in the middle frontal gyrus and 3 of 4 subjects demonstrated prominent activity in the superior and inferior frontal gyri, as well as the precentral gyri. Conclusions: Prior to seizure onset, significant biomagnetic activity was revealed in the frontal, temporal, and precentral gyri. At the start of the seizure, a transition occurred in which frontal activity predominated, with lesser activations evident in the precentral gyri. These results collectively demonstrate a progression of concurrent synchronous activity in the temporal and precentral loci prior to SWD, which leads to frontal cortical activation that occurs with absence seizures. Our results suggest that CAE is a disorder involving a cortical network that first facilitates the onset of SWD, then transitions to SWD discharges affecting a more extended cortical network.