Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI

Abstract

Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches. Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as 'ON' blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG. BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas. In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum.

Fig. 1

fMRI model derivation from EEG frequency decomposition (models 3 and 4). (a) Data from a selected contact (e.g. in the figure right amygdala showing sz onset) for the pre-ictal (− 30 s from seizure onset) and ictal phase (+ 21.2 s from seizure onset) was wavelet transformed to a representation in time (x) and frequency (y). (b) The data was convolved with a haemodynamic response and averaged within the beta and gamma bands. This procedure was repeated for each channel and the resulting regressors were entered into a design matrix (model 3). (c) A principal component analysis was performed to reduce the time-frequency data into the smallest number of regressors able to explain 90% of the data variance. These regressors were the effects of interest in model 4.

Fig. 2

Seizure-related BOLD changes based on visual segmentation of seizure (models 1 and 2). (a) Representative sample of EEG recorded during icEEG-fMRI, (i) EEG showing Ictal onset phase consisted of fast activity in beta range involving RA contacts 1–4 and RH contacts 1–2. (ii) EEG showing Late-ictal phase consisted of fast activity in gamma range involving RA contacts 1–2 and LPH contacts 4–5. (b) BOLD changes overlaid on glass brain and on a co-registered T1-volume. (i) Ictal onset phase-related BOLD clusters were seen in the right fusiform gyrus (global statistical maximum: cross-hair) in addition to other clusters in the right temporal lobe and the precuneus. (ii) Late-ictal phase-related BOLD clusters were seen in the precuneus (global statistical maximum: cross-hair) in addition to other clusters in the right temporal lobe and the posterior cingulate.

Fig. 3

Seizure-related BOLD changes based on seizure spectral dynamics (models 3 and 4). BOLD changes overlaid on glass brain (sagittal slice) and on a co-registered T1-volume. (a)(i) gamma power from all four electrode contacts showed changes in right hippocampus (red marker on sagittal slice of glass brain and cross hair on T1-volume); (ii) beta power from all four electrode contacts showed changes in left orbitofrontal cortex (red marker on sagittal slice of glass brain, cross hair on T1-volume). (b) BOLD changes for model 4: (i) all PCA components from electrode contact RH1 in right hippocampus and left orbitofrontal cortex (ii) all PCA components from electrode contact LA1 in the right fusiform gyrus and right hippocampus (iii) all PCA components from electrode contact LAH2 in the right hippocampus and right fusiform gyrus and left orbitofrontal cortex (red marks in crystal brain and crosshair correspondence).