Abstracts

Rationale: We have previously shown that slow spike and wave (SSW) and generalised paroxysmal fast activity (PFA), pathognomonic interictal discharges of Lennox-Gastaut Syndrome (LGS), heavily involve association cortex. Attention and REST (default mode) networks, are two dominant systems of association cortex. We sought to understand the interaction between these networks, and their thalamic projections, using EEG-fMRI. Methods: Eighteen subjects (11 56 yrs; 10 female) with LGS were recruited. Inclusion criteria were: 1) interictal EEG with SSW and PFA, and 2) recurrent tonic seizures on video-EEG monitoring or history. For each subject, up to 60 minutes of blood oxygen level dependent (BOLD) fMRI data (3T GE Signa LX; EPI, TR 3.2 s, TE 40 ms, 3.4mm3 voxels) were acquired during continuous EEG (in-house hardware/software). Timings of EEG discharges were used as regressors in an event-related fMRI analysis to model BOLD signal changes associated with SSW and PFA (SPM8, iBrain Analysis Toolbox). Peri-event BOLD signal time-courses were estimated from regions of interest (ROIs) placed in: a) Attention and REST'/Default mode areas, b) primary cortical structures, and c) seven thalamic nuclei identified using a tridimensional atlas of the human thalamus generated from multiple histological data (Krauth et al., 2010; Figure 1).Results: GPFA (13 subjects; 527 events totalling 745 secs) Simultaneous fMRI activity increases in 'attention' and 'REST'/default mode areas of association cortex, and pons, with primary cortical areas showing deactivation. The mediodorsal, ventral anterior and ventral lateral thalamic nuclei, as well as the anterior thalamic nucleus, show similar shaped responses to association cortex. The ventral posterior nucleus shows a similar shaped response to the sensory cortex, to which it projects. fMRI activity in the pulvinar nucleus appears to build prior to PFA, then falls once the discharge occurs. SSW (11 subjects; 3272 events totalling 2004 secs) Reduced activity in posterior cingulate, precuneus and primary cortical areas, but pre-SSW rises in fMRI activity. Anterior, mediodorsal, ventral anterior, ventral lateral, ventral posterior and pulvinar thalamic nuclei regions show fMRI changes of similar timecourse, with activity rising steeply 3-6 seconds prior to SSW, then falling abruptly once SSW appears. The centre median nucleus shows a more steady upward drift in activity prior to SSW, then a drop once the discharge occurs. Conclusions: Anterior and dorso-medial thalamic regions, which project to frontal and temporal association cortex, are activated during GPFA. The pulvinar, ventral posterior and centre median nucleus show a different shaped response, with more prominent deactivation . Thalamic responses are generally more homogeneous during SSW, with most areas activated 3-6 seconds prior to SSW. The centre median nucleus (input from brainstem reticular formation, output to basal ganglia) appears deactivated during both PFA and SSW.