Abstracts

Rationale: Rolandic epilepsy is the most common focal epilepsy syndrome, characterized by seizures and epileptiform activity arising from the perisylvian cortex. We have recently identified a focal spindle deficit in children with RE, revealing dysfunction of the thalamocortical circuit. Sleep spindles are generated by the thalamic reticular nucleus (TRN), a key structure that also modulates or “gates” thalamocortical information. Thalamocortical gating can be measured neurophysiologically using paired auditory stimuli and measuring the P50 evoked cortical responses. We hypothesized that children with RE would have impaired sensory gating, which may explain or be related to the attentional difficulties commonly reported in this disorder.

Methods: Children with RE (N=4, 3F, 13.1±3.4 years) and controls (N=8, 3F, 10.6±2.5 years) were prospectively recruited for this project. All subjects underwent magnetoencephalogram (MEG) recordings with a 306-sensor system at 2035 Hz sampling rate inside a magnetically shielded room. Subjects passively listened to ~100 paired auditory stimuli, including an initial auditory click, stimulus 1 (S1) followed by second click stimulus 2 (S2) with an interstimulus interval of 500 msec, separated by intertrial intervals of 8-10 sec. Subjects also underwent a same day high-resolution anatomical MRI. After acquisition, the data was bandpass filtered (0.5-4.5 Hz) and bad channels were marked and not considered. The data were then epoched into single trials, and epochs were rejected if the peak-to-peak amplitude during exceeded a predetermined threshold in the MEG or EOG channels. Averaged paired epochs were visualized in sensor space between -20 msec to 150 msec to confirm the P50 signal in the temporal regions in each hemisphere. MEG data were then co-registered to subject’s MRI and source estimates obtained using minimum-norm estimate (MNE) software. In source space, we identified the maximal cortical response near the sylvian fissure corresponding to the sensor space P50 (Fig1). The amplitude of the P50 response relative to the following N100 response for S1 was compared to the S2 at the same elapsed time and vertex location. The S2/S1 ratio was then modeled using linear regression with group as the predictor (active, remission, control) and subject-specific intercepts, with the hypothesis that children with RE with have reduced sensory gating.

Results: Using MEG source imaging, children with active RE (0.67±0.09 SEM) and resolved RE (0.76±0.09) have reduced sensory gating compared to controls (0.14±0.05, p< 1e-4 for both).