Nicolás von Ellenrieder

Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves

Epileptic discharges are increased during non-REM sleep. By studying the sleep EEG in patients with focal epilepsies, Frauscher et al. show that the increase is specifically associated with high-amplitude slow waves. In contrast to physiological activity, it occurs at transitions from activation to deactivation states, a period of high synchronization.

Automatic detection of fast oscillations (40–200 Hz) in scalp EEG recordings

OBJECTIVE We aim to automatically detect fast oscillations (40-200 Hz) related to epilepsy on scalp EEG recordings. METHODS The detector first finds localized increments of the signal power in narrow frequency bands. A simple classification based on two features, a narrowband to wideband signal amplitude ratio and an absolute narrowband signal amplitude, then allows for an important reduction in the number of false positives. RESULTS When compared to an expert, the performance in 15 focal epilepsy patients resulted in 3.6 false positives per minute at 95% sensitivity, with at least 40% of the detected events being true positives. In most of the patients the channels showing the highest number of events according to the expert and the automatic detector were the same. CONCLUSIONS A high sensitivity is achieved with the proposed automatic detector, but results should be reviewed by an expert to remove false positives. SIGNIFICANCE The time required to mark fast oscillations on scalp EEG recordings is drastically reduced with the use of the proposed detector. Thus, the automatic detector is a useful tool in studies aiming to create a better understanding of the fast oscillations visible on the scalp.

Approximate average head models for EEG source imaging

We examine the performance of approximate models (AM) of the head in solving the EEG inverse problem. The AM are needed when the individuals MRI is not available. We simulate the electric potential distribution generated by cortical sources for a large sample of 305 subjects, and solve the inverse problem with AM. Statistical comparisons are carried out with the distribution of the localization errors. We propose several new AM. These are the average of many individual realistic MRI-based models, such as surface-based models or lead fields. We demonstrate that the lead fields of the AM should be calculated considering source moments not constrained to be normal to the cortex. We also show that the imperfect anatomical correspondence between all cortices is the most important cause of localization errors. Our average models perform better than a random individual model or the usual average model in the MNI space. We also show that a classification based on race and gender or head size before averaging does not significantly improve the results. Our average models are slightly better than an existing AM with shape guided by measured individual electrode positions, and have the advantage of not requiring such measurements. Among the studied models, the Average Lead Field seems the most convenient tool in large and systematical clinical and research studies demanding EEG source localization, when MRI are unavailable. This AM does not need a strict alignment between head models, and can therefore be easily achieved for any type of head modeling approach.

Size of cortical generators of epileptic interictal events and visibility on scalp EEG

Growing evidence indicates that fast oscillations (>80 Hz) can be recorded interictally in the scalp EEG of patients with epilepsy, and that they may point to the seizure-onset zone. However, mechanisms underpinning the emergence of scalp fast oscillations, and whether they differ from those of interictal epileptic discharges (IEDs), are yet to be understood. The visibility of cortical electric activity on scalp EEG recordings is dependent on two factors: the characteristics of the cortical generator and the background level. We studied this issue using scalp EEG recordings and detailed simulations, with a finite element model including 8 million elements and 8 different tissues. We observed an almost linear relationship between the amplitude of scalp electric potential and the extent of the generator on the cortex. However, this relationship is subject to substantial variability, with variations in factors greater than 3 occurring simply by changing the location on the cortex of generators of fixed extent. In addition, we showed that the background power in scalp EEG recordings decreases at higher frequency bands, being inversely proportional to a power of 2.5 of the frequency. In the specific case of fast oscillations, they can be detected within the lower noise level of the ripple band (80-200 Hz) even though their median amplitude on scalp EEG recordings is more than 10 times smaller than IEDs and consistent with cortical generators of approximately 1 cm(2). In conclusion, the physics governing the propagation of electrical activity from the brain to the scalp are consistent with the hypothesis that scalp fast oscillations and intracranial high-frequency oscillations (HFOs, 80-500 Hz) are expressions of common generators. Given the potential role of HFOs as biomarkers in epilepsy, the possibility to obtain some of the associated information from scalp EEG is of high clinical significance.

Interaction with slow waves during sleep improves discrimination of physiologic and pathologic high‐frequency oscillations (80–500 Hz)

To characterize the interaction between physiologic and pathologic high‐frequency oscillations (HFOs) and slow waves during sleep, and to evaluate the practical significance of these interactions by automatically classifying channels as recording from normal or epileptic brain regions.

EEG desynchronization during phasic REM sleep suppresses interictal epileptic activity in humans

Rapid eye movement (REM) sleep has a suppressing effect on epileptic activity. This effect might be directly related to neuronal desynchronization mediated by cholinergic neurotransmission. We investigated whether interictal epileptiform discharges (IEDs) and high frequency oscillations—a biomarker of the epileptogenic zone—are evenly distributed across phasic and tonic REM sleep. We hypothesized that IEDs are more suppressed during phasic REM sleep because of additional cholinergic drive.

Scalp spindles are associated with widespread intracranial activity with unexpectedly low synchrony

In humans, the knowledge of intracranial correlates of spindles is mainly gathered from noninvasive neurophysiologic and functional imaging studies which provide an indirect estimate of neuronal intracranial activity. This potential limitation can be overcome by intracranial electroencephalography used in presurgical epilepsy evaluation. We investigated the intracranial correlates of scalp spindles using combined scalp and intracerebral depth electrodes covering the frontal, parietal and temporal neocortex, and the scalp and intracranial correlates of hippocampal and insula spindles in 35 pre-surgical epilepsy patients. Spindles in the scalp were accompanied by widespread cortical increases in sigma band energy (10–16 Hz): the highest percentages were observed in the frontoparietal lateral and mesial cortex, whereas in temporal lateral and mesial structures only a low or no simultaneous increase was present. This intracranial involvement during scalp spindles showed no consistent pattern, and exhibited unexpectedly low synchrony across brain regions. Hippocampal spindles were shorter and spatially restricted with a low synchrony even within the temporal lobe. Similar results were found for the insula. We suggest that the generation of spindles is under a high local cortical influence contributing to the concept of sleep as a local phenomenon and challenging the notion of spindles as widespread synchronous oscillations.

Detection and Magnetic Source Imaging of Fast Oscillations (40–160 Hz) Recorded with Magnetoencephalography in Focal Epilepsy Patients

AbstractWe present a framework to detect fast oscillations (FOs) in magnetoencephalography (MEG) and to perform magnetic source imaging (MSI) to determine the location and extent of their generators in the cortex. FOs can be of physiologic origin associated to sensory processing and memory consolidation. In epilepsy, FOs are of pathologic origin and biomarkers of the epileptogenic zone. Seventeen patients with focal epilepsy previously confirmed with identified FOs in scalp electroencephalography (EEG) were evaluated. To handle data deriving from large number of sensors (275 axial gradiometers) we used an automatic detector with high sensitivity. False positives were discarded by two human experts. MSI of the FOs was performed with the wavelet based maximum entropy on the mean method. We found FOs in 11/17 patients, in only one patient the channel with highest FO rate was not concordant with the epileptogenic region and might correspond to physiologic oscillations. MEG FOs rates were very low: 0.02–4.55 per minute. Compared to scalp EEG, detection sensitivity was lower, but the specificity higher in MEG. MSI of FOs showed concordance or partial concordance with proven generators of seizures and epileptiform activity in 10/11 patients. We have validated the proposed framework for the non-invasive study of FOs with MEG. The excellent overall concordance with other clinical gold standard evaluation tools indicates that MEG FOs can provide relevant information to guide implantation for intracranial EEG pre-surgical evaluation and for surgical treatment, and demonstrates the important added value of choosing appropriate FOs detection and source localization methods.

Sleep influences the intracerebral EEG pattern of focal cortical dysplasia

Highlights • We analyze the distribution of intracerebral EEG patterns of FCD in relation to sleep.• FCD interictal EEG patterns are present between 45% and 97% of the time analyzed.• Despite almost continuous spiking, sleep is an important modulator of FCD EEG patterns.• This suggests that dysplastic tissue is under thalamocortical control.

Extent of cortical generators visible on the scalp: Effect of a subdural grid

The effect of the non-conducting substrate of a subdural grid on the scalp electric potential distribution is studied through simulations. Using a detailed head model and the finite element method we show that the governing physics equations predict an important attenuation in the scalp potential for generators located under the grid, and an amplification for generators located under holes in the skull filled with conductive media. These effects are spatially localized and do not cancel each other. A 4 × 8 cm grid can produce attenuations of 2 to 3 times, and an 8 × 8 cm grid attenuation of up to 8 times. As a consequence, when there is no subdural grid, generators of 4 to 8 cm(2) produce scalp potentials of the same maximum amplitude as generators of 10 to 20 cm(2) under the center of a subdural grid. This means that the minimum cortical extents necessary to produce visible scalp activity determined from simultaneous scalp and subdural recordings can be overestimations.