Pierre LeVan

Interictal high‐frequency oscillations (80–500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain

Purpose:  High‐frequency oscillations (HFOs) known as ripples (80–250 Hz) and fast ripples (250–500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels.

High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type

High frequency oscillations (HFOs) called ripples (80-250 Hz) and fast ripples (FR, 250-500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80-250 Hz) and Fast Ripples (250-500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.

Effect of sleep stage on interictal high-frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy.

Purpose:  To investigate the effect of sleep stage on the properties of high‐frequency oscillations (HFOs) recorded from depth macroelectrodes in patients with focal epilepsy.

A system for automatic artifact removal in ictal scalp EEG based on independent component analysis and Bayesian classification

OBJECTIVE To devise an automated system to remove artifacts from ictal scalp EEG, using independent component analysis (ICA). METHODS A Bayesian classifier was used to determine the probability that 2s epochs of seizure segments decomposed by ICA represented EEG activity, as opposed to artifact. The classifier was trained using numerous statistical, spectral, and spatial features. The systems performance was then assessed using separate validation data. RESULTS The classifier identified epochs representing EEG activity in the validation dataset with a sensitivity of 82.4% and a specificity of 83.3%. An ICA component was considered to represent EEG activity if the sum of the probabilities that its epochs represented EEG exceeded a threshold predetermined using the training data. Otherwise, the component represented artifact. Using this threshold on the validation set, the identification of EEG components was performed with a sensitivity of 87.6% and a specificity of 70.2%. Most misclassified components were a mixture of EEG and artifactual activity. CONCLUSIONS The automated system successfully rejected a good proportion of artifactual components extracted by ICA, while preserving almost all EEG components. The misclassification rate was comparable to the variability observed in human classification. SIGNIFICANCE Current ICA methods of artifact removal require a tedious visual classification of the components. The proposed system automates this process and removes simultaneously multiple types of artifacts.

Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study

Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD patients may help to understand the role of the lesion in epileptogenesis and also determine the potential surgical target.

Absence seizures: Individual patterns revealed by EEG‐fMRI

Purpose:  Absences are characterized by an abrupt onset and end of generalized 3–4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography–functional magnetic resonance imaging (EEG–fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences.

Hemodynamic changes preceding the interictal EEG spike in patients with focal epilepsy investigated using simultaneous EEG-fMRI

EEG-fMRI is a non-invasive technique that allows the investigation of epileptogenic networks in patients with epilepsy. Lately, BOLD changes occurring before the spike were found in patients with generalized epilepsy. The study of metabolic changes preceding spikes might improve our knowledge of spike generation. We tested this hypothesis in patients with idiopathic and symptomatic focal epilepsy. Eleven consecutive patients were recorded at 3 T: five with idiopathic focal and 6 with symptomatic focal epilepsy. Thirteen spike types were analyzed separately. Statistical analysis was performed using the timing of spikes as events, modeled with HRFs peaking between -9 s and +9 s around the spike. HRFs were calculated the most focal BOLD response. Eleven of the thirteen studies showed prespike BOLD responses. Prespike responses were more focal than postspike responses. Three studies showed early positive followed by later negative BOLD responses in the spike field. Three had early positive BOLD responses in the spike field, which remained visible in the later maps. Three others had positive BOLD responses in the spike field, later propagating to surrounding areas. HRFs peaked between -5 and +6 s around the spike timing. No significant EEG changes could be identified prior to the spike. BOLD changes prior to the spike frequently occur in focal epilepsies. They are more focal than later BOLD changes and strongly related to the spike field. Early changes may result from increased neuronal activity in the spike field prior to the EEG spike and reflect an event more localized than the spike itself.

High-frequency intracerebral EEG activity (100-500 Hz) following interictal spikes

Summary:  Purpose: High‐frequency activity has been recorded with intracerebral microelectrodes in epileptic patients and related to seizure genesis. Our goal was to analyze high‐frequency activity recorded with electroencephalograph (EEG) macroelectrodes during the slow wave immediately following interictal spikes, given the potential importance of this presumed hyperpolarization in transforming spikes into seizures.

EEG-fMRI Adding to standard evaluations of patients with nonlesional frontal lobe epilepsy

Objective: In patients with nonlesional frontal lobe epilepsy (FLE), the delineation of the epileptogenic zone is difficult. Therefore these patients are often not considered for surgery due to an unclear seizure focus. The aim of this study was to investigate whether EEG-fMRI can add useful information in the preoperative evaluation of these patients. Methods: Nine nonlesional FLE patients were studied with EEG-fMRI using a 3 T scanner. Spike-related blood oxygen level dependent (BOLD) signal changes were compared to the topography of the spikes and to PET and SPECT results if available. The structural MRIs were reviewed for subtle abnormalities in areas that showed BOLD responses. For operated patients, postoperative resection and histology were compared to BOLD responses. Results: Concordance between spike localization and positive BOLD response was found in 8 patients. PET and SPECT investigations corresponded with BOLD signal changes in 6 of 7 investigations. In 2 cases, reviewing the structural MRI guided by EEG-fMRI data resulted in considering a suspicious deep sulcus. Two patients were operated. In 1, the resected cortex corresponded with the suspicious sulcus and fMRI results and histology showed cortical dysplasia. In another, histology revealed an extended microdysgenesis not visible on structural MRI. EEG-fMRI had shown activation just adjacent to the resected pathologic area. Conclusions: Our study provides different types of support (topography, concordance with PET and SPECT, structural peculiarities, postoperative histology) that EEG-fMRI may help to delineate the epileptic focus in patients with nonlesional frontal lobe epilepsy, a challenging group in the preoperative evaluation.

Tracking dynamic resting-state networks at higher frequencies using MR-encephalography.

Current resting-state network analysis often looks for coherent spontaneous BOLD signal fluctuations at frequencies below 0.1 Hz in a multiple-minutes scan. However hemodynamic signal variation can occur at a faster rate, causing changes in functional connectivity at a smaller time scale. In this study we proposed to use MREG technique to increase the temporal resolution of resting-state fMRI. A three-dimensional single-shot concentric shells trajectory was used instead of conventional EPI, with a TR of 100 ms and a nominal spatial resolution of 4 × 4 × 4 mm(3). With this high sampling rate we were able to resolve frequency components up to 5 Hz, which prevents major physiological noises from aliasing with the BOLD signal of interest. We used a sliding-window method on signal components at different frequency bands, to look at the non-stationary connectivity maps over the course of each scan session. The aim of the study paradigm was to specifically observe visual and motor resting-state networks. Preliminary results have found corresponding networks at frequencies above 0.1 Hz. These networks at higher frequencies showed better stability in both spatial and temporal dimensions from the sliding-window analysis of the time series, which suggests the potential of using high temporal resolution MREG sequences to track dynamic resting-state networks at sub-minute time scale.