Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI

Department of Neurology, University of Cincinnati Medical Center, Cincinnati, OH 45267-0525, USA.
Epilepsy & Behavior (Impact Factor: 2.26). 08/2010; 18(4):404-13. DOI: 10.1016/j.yebeh.2010.05.009
Source: PubMed


In patients with idiopathic generalized epilepsies (IGEs), bursts of generalized spike and wave discharges (GSWDs) lasting > or =2 seconds are considered absence seizures. The location of the absence seizures generators in IGEs is thought to involve interplay between various components of thalamocortical circuits; we have recently postulated that medication resistance may, in part, be related to the location of the GSWD generators [Szaflarski JP, Lindsell CJ, Zakaria T, Banks C, Privitera MD. Epilepsy Behav. 2010;17:525-30]. In the present study we hypothesized that patients with medication-refractory IGE (R-IGE) and continued absence seizures may have GSWD generators in locations other than the thalamus, as typically seen in patients with IGE. Hence, the objective of this study was to determine the location of the GSWD generators in patients with R-IGE using EEG/fMRI. Eighty-three patients with IGE received concurrent EEG/fMRI at 4 T. Nine of them (aged 15-55) experienced absence seizures during EEG/fMRI and were included; all were diagnosed with R-IGE. Subjects participated in up to three 20-minute EEG/fMRI sessions (400 volumes, TR=3 seconds) performed at 4 T. After removal of fMRI and ballistocardiographic artifacts, 36 absence seizures were identified. Statistical parametric maps were generated for each of these sessions correlating seizures to BOLD response. Timing differences between brain regions were tested using statistical parametric maps generated by modeling seizures with onset times shifted relative to the GSWD onsets. Although thalamic BOLD responses peaked approximately 6 seconds after the onset of absence seizures, other areas including the prefrontal and dorsolateral cortices showed brief and nonsustained peaks occurring approximately 2 seconds prior to the maximum of the thalamic peak. Temporal lobe peaks occurred at the same time as the thalamic peak, with a cerebellar peak occurring approximately 1 second later. Confirmatory analysis averaging cross-correlation between cortical and thalamic regions of interest across seizures corroborated these findings. Finally, Granger causality analysis showed effective connectivity directed from frontal lobe to thalamus, supporting the notion of earlier frontal than thalamic involvement. The results of this study support our original hypothesis and indicate that in the patients with R-IGE studied, absence seizures may be initiated by widespread cortical (frontal and parietal) areas and sustained in subcortical (thalamic) regions, suggesting that the examined patients have cortical onset epilepsy with propagation to thalamus.

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    • "Several EEG–fMRI studies gave insights into the widespread networks involved in the generation of SWD showing significant changes in fMRI BOLD signal during SWD in the thalamus and cortical areas, mostly including the frontal, parieto-occipital cortices and the limbic system (Moeller et al., 2008, 2013; Tyvaert et al., 2009; Szaflarski et al., 2010; Masterton et al., 2013). Albeit fMRI results can give novel insights into the pathophysiology of CAE, the poor temporal resolution of this technique prevents any estimate on the fast dynamical properties of SWD. "
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    ABSTRACT: Objective: We investigated interictal EEG activity in patients with childhood absence seizures with the aim of detecting markers of network defects generating "idiopathic" hyperexcitability in this form of epilepsy. Methods: We included 11 drug-naïve patients with childhood absence epilepsy (CAE), and 11 age matched controls (CTRL). We analyzed interictal EEG using partial directed coherence (PDC), a connectivity estimator in frequency domain based on autoregressive multivariate (MVAR) modeling giving the advantage of indicating the direction and strength of the interactions between multiple variables. Results: Our results revealed the presence of an abnormal cortico-cortical network occurring in the interictal condition in CAE and involving a large span of frequencies, with prominence in the alpha band; the most evident finding was a highly significant increase of out-going connectivity involving frontal and central cortical areas in CAE patients compared to CTRL subjects. Conclusions: Our observation indicates that, in interictal conditions, a distorted network characterizes CAE, and a hyperconnected network is already detectable under resting conditions in the delta, theta and alpha bands. Significance: The increased interictal EEG connectivity demonstrated here provides support for a persistent abnormal relationship between the thalamus and a hyperexcitable cortex outside the ictal phase.
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    • "More specifically, causality may be evaluated by comparing the variance of the residuals after an autoregressive (AR) application to the reference signal “A”, with the same variance being obtained when autoregression is evaluated on the past values of the signal “A” and the past values of the potentially causing signal “B”. GCA has been shown to be a viable technique for analyzing fMRI data [47]–[49] and to not vary after filtering [50]. Analysis of effective connectivity between the independent components was thus conducted using GCA, which models directional causality among multiple time series based on a variable autoregressive model [51]. "
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    • "Recently, in order to characterize the abnormal information flow, some approaches have been used in epilepsy patients or experimental protocols, such as non-linear regression [24]–[28], dynamic causal modeling [29]–[31] and Granger causality analysis (GCA) [32]–[35]. GCA has been proved helpful to identify the direction of seizure propagation [35], [36]. In a region-of-interest (ROI) based research, Morgan et al. [34] performed GCA between bilateral hippocampus in mTLE. "
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