The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks. METHODS: We analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level. RESULTS: We found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our finding may help understand networks related to a more "isolated" epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.

Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth.

Time-varying effective EEG source connectivity: the optimization of model parameters.

Adaptive estimation methods based on general Kalman filter are powerful tools to investigate brain networks dynamics given the non-stationary nature of neural signals. These methods rely on two parameters, the model order p and adaptation constant c, which determine the resolution and smoothness of the time-varying multivariate autoregressive estimates. A sub-optimal filtering may present consistent biases in the frequency domain and temporal distortions, leading to fallacious interpretations. Thus, the performance of these methods heavily depends on the accurate choice of these two parameters in the filter design. In this work, we sought to define an objective criterion for the optimal choice of these parameters. Since residual- and information-based criteria are not guaranteed to reach an absolute minimum, we propose to study the partial derivatives of these functions to guide the choice of p and c. To validate the performance of our method, we used a dataset of human visual evoked potentials during face perception where the generation and propagation of information in the brain is well understood and a set of simulated data where the ground truth is available.

From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging.

While many insights on brain development and aging have been gained by studying resting-state networks with fMRI, relating these changes to cognitive functions is limited by the temporal resolution of fMRI. In order to better grasp short-lasting and dynamically changing mental activities, an increasing number of studies utilize EEG to define resting-state networks, thereby often using the concept of EEG microstates. These are brief (around 100 ms) periods of stable scalp potential fields that are influenced by cognitive states and are sensitive to neuropsychiatric diseases. Despite the rising popularity of the EEG microstate approach, information about age changes is sparse and nothing is known about sex differences. Here we investigated age and sex related changes of the temporal dynamics of EEG microstates in 179 healthy individuals (6-87 years old, 90 females, 204-channel EEG). We show strong sex-specific changes in microstate dynamics during adolescence as well as at older age. In addition, males and females differ in the duration and occurrence of specific microstates. These results are of relevance for the comparison of studies in populations of different age and sex and for the understanding of the changes in neuropsychiatric diseases.

Comparison of high gamma electrocorticography and fMRI with electrocortical stimulation for localization of somatosensory and language cortex.

OBJECTIVE: We investigated the contribution of electrocortical stimulation (ECS), induced high gamma electrocorticography (hgECoG) and functional magnetic resonance imaging (fMRI) for the localization of somatosensory and language cortex. METHODS: 23 Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task. 14 Patients did the same protocol with fMRI prior to implantation. RESULTS: ECS resulted in the identification of thumb somatosensory cortex in 12/16 patients. Taking ECS as a gold standard, hgECoG and fMRI identified 53.6/33% of true positive and 4/12% of false positive contacts, respectively. The hgECoG false positive sites were all found in the hand area of the post-central gyrus. ECS localized language-related sites in 7/12 patients with hgECoG and fMRI showing 50/64% of true positive and 8/23% of false positive contacts, respectively. All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas. Four patients showed post-surgical impairments: the resection included the sites positively indicated by ECS, hgECoG and fMRI in 3 patients and a positive hgECoG site in one patient. CONCLUSIONS: HgECoG and fMRI provide additional localization information in patients who cannot sufficiently collaborate during ECS. SIGNIFICANCE: HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible, but also when ECS does not provide any result.

Validity and Repeatability of Saccadic Response Times Across the Visual Field in Eye Movement Perimetry.

PURPOSE: To assess the validity and repeatability of saccadic reaction times (SRT) across the visual field up to 30° using eye movement perimetry (EMP). METHODS: Eighteen subjects (36 eyes) were shown a central stimulus on a flat monitor screen. Next, peripheral stimuli were shown using an overlap paradigm. Subjects were instructed to look at detected peripheral stimuli and then refixate the central stimulus again. In three repetitive measurement series, a total of 288 visual stimuli (3 series × 24 locations × 4 contrast levels) were presented. Levene's test for equality of variances was applied to test the effect of stimulus location and measurement series on SRT variance. A Wilcoxon signed ranks test was used to compare SRTs between measurement series. RESULTS: A total of 26 eyes were included in the study (72%). On average, 90.5% of the peripheral stimuli were labeled as 'seen' based on eye movement responses. Between the series, the mean SD of SRT differences was approximately 100 ms. Significantly faster SRTs were only found at contrast level 0.8 in series III compared with series II. In series I, SRT variance was independent in 75% of all locations. Across the three series, SRT variance was independent in 87.5% of all locations. CONCLUSIONS: The present study demonstrates low variability of SRT across the visual field up to 30° eccentricity and across measurement series. TRANSLATIONAL RELEVANCE: SRT as a measure for visual field responsiveness may be a potential marker to detect risk areas in specific parts of the visual field.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.

Spatio-temporal dynamics of olfactory processing in the human brain: an event-related source imaging study.

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H(2)S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution.

Continuous EEG source imaging enhances analysis of EEG-fMRI in focal epilepsy.

INTRODUCTION: EEG-correlated fMRI (EEG-fMRI) studies can reveal haemodynamic changes associated with Interictal Epileptic Discharges (IED). Methodological improvements are needed to increase sensitivity and specificity for localising the epileptogenic zone. We investigated whether the estimated EEG source activity improved models of the BOLD changes in EEG-fMRI data, compared to conventional << event-related >> designs based solely on the visual identification of IED. METHODS: Ten patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI. EEG Source Imaging (ESI) was performed on intra-fMRI averaged IED to identify the irritative zone. The continuous activity of this estimated IED source (cESI) over the entire recording was used for fMRI analysis (cESI model). The maps of BOLD signal changes explained by cESI were compared to results of the conventional IED-related model. RESULTS: ESI was concordant with non-invasive data in 13/15 different types of IED. The cESI model explained significant additional BOLD variance in regions concordant with video-EEG, structural MRI or, when available, intracranial EEG in 10/15 IED. The cESI model allowed better detection of the BOLD cluster, concordant with intracranial EEG in 4/7 IED, compared to the IED model. In 4 IED types, cESI-related BOLD signal changes were diffuse with a pattern suggestive of contamination of the source signal by artefacts, notably incompletely corrected motion and pulse artefact. In one IED type, there was no significant BOLD change with either model. CONCLUSION: Continuous EEG source imaging can improve the modelling of BOLD changes related to interictal epileptic activity and this may enhance the localisation of the irritative zone.

The spatio-temporal mapping of epileptic networks: combination of EEG-fMRI and EEG source imaging.

Simultaneous EEG-fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG-fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG-fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG-fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks.

Intracerebral recordings of nocturnal hyperkinetic seizures: demonstration of a longer duration of the pre-seizure sleep spindle.

OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) seizures occur primarily during non-rapid eye movement sleep stage 2. We observed in several patients rhythms of same localization and frequency as sleep spindles, immediately preceding and sometimes continuing at seizure onsets. We aimed to study the link between sleep spindles and seizure onsets. METHODS: We used intracerebral stereo-EEG ictal recordings of two MRI-negative patients with clinically defined NFLE. For each of the six studied seizures, sustained activity in the frontal sleep spindle frequency (12Hz) was observed around seizure onset. The duration of this pre-seizure sleep spindle was compared to that of the 10 preceding sleep spindles. RESULTS: The pre-seizure sleep spindles were clearly of longer duration than the "interictal" sleep spindles for all seizures. This sustained pre-seizure 12Hz activity could be differentiated from normal awakenings, and showed no spatial relation to the ictal onset. CONCLUSIONS: We demonstrated a functional alteration of the sleep spindle-generating thalamocortical loop concomitant with the seizure onsets. This defect may also be involved in seizure generation. SIGNIFICANCE: A thalamic participation in NFLE pathogenesis is likely in our two patients. The study of additional patients will allow to evaluate the role of the thalamocortical circuits in NFLE.

Sex differences in semantic processing: event-related brain potentials distinguish between lower and higher order semantic analysis during word reading.

Behavioral studies suggest that women and men differ in the strategic elaboration of verbally encoded information especially in the absence of external task demand. However, measuring such covert processing requires other than behavioral data. The present study used event-related potentials to compare sexes in lower and higher order semantic processing during the passive reading of semantically related and unrelated word pairs. Women and men showed the same early context effect in the P1-N1 transition period. This finding indicates that the initial lexical-semantic access is similar in men and women. In contrast, sexes differed in higher order semantic processing. Women showed an earlier and longer lasting context effect in the N400 accompanied by larger signal strength in temporal networks similarly recruited by men and women. The results suggest that women spontaneously conduct a deeper semantic analysis. This leads to faster processing of related words in the active neural networks as reflected in a shorter stability of the N400 map in women. Taken together, the findings demonstrate that there is a selective sex difference in the controlled semantic analysis during passive word reading that is not reflected in different functional organization but in the depth of processing.

Speech arrest with stimulation may not reliably predict language deficit after epilepsy surgery.

The authors present a patient in whom electrical cortical stimulation of the posterior temporal cortex induced speech arrest, comprehension deficits, and other language-related impairments. This area was ultimately resected because of persistence of a severe seizure disorder. No postoperative aphasia was observed despite the cortical stimulation results, and the patient is since seizure free. These findings question the well-established principle that corticography directly reflects local cortical functions in all patients.

Patients with extratemporal lobe epilepsy do not differ from healthy subjects with respect to subcortical volumes.

BACKGROUND: Evidence from previous volumetric magnetic resonance studies has revealed that patients with chronic temporal lobe epilepsy show atrophy of distinct subcortical nuclei, predominantly ipsilateral to the focus side. We were interested to find out if there is also selective subcortical atrophy in patients suffering from long standing extratemporal lobe epilepsy. METHODS: Thirty one patients in whom pre-surgical evaluation unambiguously localised an extratemporal focus were included in this study. Using high resolution magnetic resonance imaging, the volumes of the caudate nuclei, putamen, pallidum, and thalamus were measured bilaterally in both hemispheres and compared with measurements obtained in 15 healthy volunteers. RESULTS: No significant difference in volumes was found between the two subject groups, or in any subgroup of extratemporal lobe epilepsy patients, nor was there any relation to clinical variables such as age of onset, overall seizure frequency, or disease duration. However, patients who had no or only rare generalised tonic-clonic seizures seemed to differ from the other patients and controls in that they had smaller putamen volumes bilaterally (p<0.001). CONCLUSION: We concluded that extratemporal lobe epilepsy in general is not associated with diminished volumes in the studied subcortical structures, which contrasts with findings in temporal lobe epilepsy patients. Thus, both entities differ both cortically and subcortically. However, we found that small putamen volume was bilaterally associated with absent or rare generalised tonic-clonic seizures, implicating the putamen in the control of the most disabling seizure type, independent of the site of neocortical focus.

Pure imagery hemi-neglect of far space.

Patients with hemispatial neglect restricted to near (within reaching distance) or to far space (beyond reaching distance) have been described. This constitutes a double-dissociation considered by current neurocognitive thinking as compelling evidence for separate networks. However, a similar double-dissociation exists with respect to perceived as opposed to imagined space. If the organization of represented space was similar to that of perceived space, it should contain a far/near dissociation as well. This paper describes a patient with pure representational neglect restricted to far space.

Face versus non-face object perception and the 'other-race' effect: a spatio-temporal event-related potential study.

OBJECTIVE: To investigate a modulation of the N170 face-sensitive component related to the perception of other-race (OR) and same-race (SR) faces, as well as differences in face and non-face object processing, by combining different methods of event-related potential (ERP) signal analysis. METHODS: Sixty-two channel ERPs were recorded in 12 Caucasian subjects presented with Caucasian and Asian faces along with non-face objects. Surface data were submitted to classical waveforms and ERP map topography analysis. Underlying brain sources were estimated with two inverse solutions (BESA and LORETA). RESULTS: The N170 face component was identical for both race faces. This component and its topography revealed a face specific pattern regardless of race. However, in this time period OR faces evoked significantly stronger medial occipital activity than SR faces. Moreover, in terms of maps, at around 170 ms face-specific activity significantly preceded non-face object activity by 25 ms. These ERP maps were followed by similar activation patterns across conditions around 190-300 ms, most likely reflecting the activation of visually derived semantic information. CONCLUSIONS: The N170 was not sensitive to the race of the faces. However, a possible pre-attentive process associated to the relatively stronger unfamiliarity for OR faces was found in medial occipital area. Moreover, our data provide further information on the time-course of face and non-face object processing.

Mapping of the neuronal networks of human cortical brain functions.

OBJECTIVE: The principles and methodology of event-related fMRI, electromagnetic source imaging and intracranial evoked potentials will be described along with some examples of the mapping of the neuronal networks of human cortical brain functions with the use of these techniques. INTRODUCTION: Functional brain mapping using PET or fMRI has provided clues on the functioning brain and notably on the functional neuroanatomy of cognitive functions. These mapping possibilities can be used to delineate in an individual patient the brain areas subserving a cerebral function that might be compromised by a surgery in a nearby location, or to target a functional neurosurgical procedure. BACKGROUND: Brain functions and notably "higher brain functions" are served by a complex network of interrelating brain regions. Deeper insights into the functioning of a neuronal network can be gained by adding dynamic, i.e. temporal, information to the functional maps. This will demonstrate the orchestration of the activation of the different brain areas constituting the network, which gives clues to the information processing and therefore to the functioning of the different modules of the network. In order to track the flow of information and the sequential activation of the different brain regions constituting the network, brain activity has to be recorded at the speed of transfer of activation from one neuronal population to the other. The temporal resolution needed to achieve this is not in the range of traditional subtractive or comparative PET or fMRI techniques. NEW DEVELOPMENTS: Novel fMRI methods that record haemodynamic signal changes after single events (event-related fMRI) are now able to determine sequential neural processing by distinguishing the relative onset-time of activity between different areas. The temporal resolution of event-related (ER) fMRI is sufficient to detect changes of mental activity within the order of several hundreds of milliseconds. This allows the exploration of a broad range of cognitive functions. Nevertheless, this technique is currently not rapid enough to observe the transient coordinations and oscillations of neuronal activities occurring across certain cortical areas during the performance of cognitive tasks. The temporal resolution needed for that is within the order of tens or a few milliseconds and is only accessible by EEG or MEG that allow true real-time measurements of the neuronal activity elicited by a stimulus. Surface recordings of multichannel EEG or MEG combined with novel electromagnetic source localisation algorithms allow a relatively precise estimation of the activated areas. A more direct localisation of electric activity is achieved by intracranial recordings in patients having implanted electrodes for diagnostic reasons. In these cases, a high temporal and spatial resolution is achieved but with a limited sampling of brain regions. CONCLUSION: Although the temporal resolution of ER fMRI is due to improve, the temporal measures provided by EEG, MEG or intracranial event-related potentials (ERPs) are absolute, which remains a unique feature of these techniques. Therefore, ER fMRI and electromagnetic source imaging are complementary. The maps obtained with ER fMRI may be refined by electromagnetic ERPs that provide further insights into the temporal coordination or orchestration between the cortical areas already detected by ER fMRI and constituting a neuronal network, and ER fMRI can be used to precisely locate the areas coarsely situated and delineated by electromagnetic source imaging. Thus, the combination of ER fMRI and electromagnetic ERPs is essential in order to produce a mapping method with a millimetre spatial resolution and a millisecond temporal resolution. Future applications should combine these techniques to localise precisely and non-invasively relevant sensory, motor and cognitive processes in order to adequately tailor any brain surgery.

Epileptic source localization with high density EEG: how many electrodes are needed?

OBJECTIVE: Electroencephalography (EEG) source reconstruction is becoming recognized as a useful technique to non-invasively localize the epileptic focus. Whereas, large array magnetoencephalography (MEG) systems are available since quite some time, application difficulties have previously prevented multichannel EEG recordings. Recently, however, EEG systems which allow for quick (10-20min) application of, and recording from, up to 125 electrodes have become available. The purpose of the current investigation was to systematically compare the accuracy of epileptic source localization with high electrode density to that obtained with sparser electrode setups. METHODS: Interictal epileptiform activity was recorded with 123 electrodes in 14 epileptic patients undergoing presurgical evaluation. Each single epileptiform potential was down sampled to 63 and 31 electrodes, and a distributed source model (EPIFOCUS) was used to reconstruct the sources with the 3 different electrode configurations. The localization accuracy with the 3 electrode setups was then assessed, by determining the distance from the inverse solution, maximum of each single spike to the epileptogenic lesion. RESULTS: In 9/14 patients, the distance from the EEG source to the lesion was significantly smaller with 63 than with 31 electrodes, and increasing the number of electrodes to 123 increased this number of patients from 9 to 11. Simulations confirmed the relation between the number of electrodes and localization accuracy. CONCLUSIONS: The results illustrate the necessity of multichannel EEG recordings for high source location accuracy in epileptic patients.

[Variability of right hemisphere activation during semantic word processing in aphasic patients: an electrophysiologic study in three patients]. / Variabilité de l'activation hémisphérique droite lors du traitement sémantique des mots chez des patients aphasiques: étude électrophysiologique de trois cas.

After stroke, the interhemispheric reorganisation of the neural network implicated in language is hypothesized to be a function not only of the site of lesion but also of the residual impairment. With a multiple case approach, we tested this hypothesis in three chronic aphasic patients. Two patients, GE (capsulo-lenticular stroke) and JHN (fronto-temporal stroke) showed formal residual semantic difficulties, while the third patient (EG, large sylvian lesion) did not. Brain electric activity was analysed during a categorisation task of tachistoscopically presented words in the left and the right visual field. The temporal analysis of brain activity showed that both patients with semantic residual difficulties activated the right hemisphere (RH) during some steps of word processing. In the third patient, without semantic impairment, the RH was activated only during a short time period. Further more, RH activation was shown to be dependent on the visual field of word presentation. Phonological impairment was not predictive of RH activation. These results suggest that RH activation, particularly anterior regions, can occur during semantic processing of words as a function of semantic residual impairment.