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Background: Awareness is a state of consciousness that enables a subject to interact with the environment. Transient alteration of awareness (AA) is a disabling sign of many types of epileptic seizures. The brain mechanisms of awareness and its alteration are not well known. Objective/Hypothesis: Transient and isolated AA induced by electrical brain stimulation during a stereoelectroencephalography (SEEG) recording represents an ideal model for studying the associated modifications of functional connectivity and locating the hubs of awareness networks. Methods: We investigated the SEEG signals-based brain functional connectivity (FC) changes vs background occurring during AA triggered by three thalamic and two insular stimulations in three patients explored by SEEG in the frame of presurgical evaluation for focal drug-resistant epilepsy. The results were compared to the stimulations of the same sites that did not induce clinical changes (negative stimulations). Results: We observed decreased node strength in the pulvinar, insula, and parietal associative cortices during the thalamic and insular stimulations that induced AA. The link strengths characterizing functional coupling between the thalamus and the insular, prefrontal, temporal, or parietal associative cortices were also decreased. In contrast, there was an increased synchronization between the precuneus and the temporal lateral cortex. These FC changes were absent during the negative stimulations. Conclusion: Our study highlights the role of the pulvinar, insular, and parietal hubs in maintaining the awareness networks and paves the way for invasive or non-invasive neuromodulation protocols to reduce AA manifestations during epileptic seizures.

Abstract The postictal state, an abnormal cerebral condition following a seizure until the return to the interictal baseline, is frequently overlooked, despite often exceeding ictal duration and significantly impacting patients' lives. This study analyzes stereo‐EEG (SEEG) signal dynamics using permutation entropy to quantify recovery time (postictal alteration time – PAT) in focal epilepsy and its clinical correlations. The average PAT was 4.5 min, extending up to an hour and was highest in temporal epilepsy and hippocampal sclerosis. Correlating with age at seizure onset and at SEEG, PAT provides a solution for operationally defining the postictal state and guiding interventions.

Abstract Stereoelectroencephalography is a powerful intracerebral EEG recording method for the presurgical evaluation of epilepsy. It consists in implanting depth electrodes in the patient’s brain to record electrical activity and map the epileptogenic zone, which should be resected to render the patient seizure-free. Stereoelectroencephalography has high spatial accuracy and signal-to-noise ratio but remains limited in the coverage of the explored brain regions. Thus, the implantation might provide a suboptimal sampling of epileptogenic regions. We investigate the potential of improving a suboptimal stereoelectroencephalography recording by performing source localization on stereoelectroencephalography signals. We propose combining independent component analysis, connectivity measures to identify components of interest, and distributed source modelling. This approach was tested on two patients with two implantations each, the first failing to characterize the epileptogenic zone and the second giving a better diagnosis. We demonstrate that ictal and interictal source localization performed on the first stereoelectroencephalography recordings matches the findings of the second stereo-EEG exploration. Our findings suggest that independent component analysis followed by source localization on the topographies of interest is a promising method for retrieving the epileptogenic zone in case of suboptimal implantation.

Various methods have been proposed to characterize the functional connectivity between nodes in a network measured with different modalities (electrophysiology, functional magnetic resonance imaging etc.). Since different measures of functional connectivity yield different results for the same dataset, it is important to assess when and how they can be used. In this work, we provide a systematic framework for evaluating the performance of a large range of functional connectivity measures – based upon a comprehensive portfolio of models generating measurable responses. Specifically, we benchmarked 42 methods using 10,000 simulated datasets from 5 different types of generative models with different connectivity structures. Since all functional connectivity methods require the setting of some parameters (window size and number, model order etc.), we first optimized these parameters using performance criteria based upon (threshold free) ROC analysis. We then evaluated the performance of the methods on data simulated with different types of models. Finally, we assessed the performance of the methods against different levels of signal-to-noise ratios and network configurations. A MATLAB toolbox is provided to perform such analyses using other methods and simulated datasets.

Abstract Objective Stereoelectroencephalography (SEEG) is the reference method in the presurgical exploration of drug‐resistant focal epilepsy. However, prognosticating surgery on an individual level is difficult. A quantified estimation of the most epileptogenic regions by searching for relevant biomarkers can be proposed for this purpose. We investigated the performances of ictal (Epileptogenicity Index, EI; Connectivity EI, cEI), interictal (spikes, high‐frequency oscillations, HFO [80–300 Hz]; Spikes × HFO), and combined (Spikes × EI; Spikes × cEI) biomarkers in predicting surgical outcome and searched for prognostic factors based on SEEG‐signal quantification. Methods Fifty‐three patients operated on following SEEG were included. We compared, using precision‐recall, the epileptogenic zone quantified using different biomarkers (EZq) against the visual analysis (EZC). Correlations between the EZ resection rates or the EZ extent and surgical prognosis were analyzed. Results EI and Spikes × EI showed the best precision against EZc (0.74; 0.70), followed by Spikes × cEI and cEI, whereas interictal markers showed lower precision. The EZ resection rates were greater in seizure‐free than in non‐seizure‐free patients for the EZ defined by ictal biomarkers and were correlated with the outcome for EI and Spikes × EI. No such correlation was found for interictal markers. The extent of the quantified EZ did not correlate with the prognosis. Interpretation Ictal or combined ictal–interictal markers overperformed the interictal markers both for detecting the EZ and predicting seizure freedom. Combining ictal and interictal epileptogenicity markers improves detection accuracy. Resection rates of the quantified EZ using ictal markers were the only statistically significant determinants for surgical prognosis.

Low-gamma (25-45 Hz) and theta (4-8 Hz) oscillations are proposed to underpin the integration of phonemic and syllabic information, respectively. How these two scales of analysis split functions across hemispheres is unclear. We analyzed cortical responses from an epileptic patient with a rare bilateral electrode implantation (stereotactic EEG) in primary (A1/BA41 and A2/BA42) and association auditory cortices (BA22). Using time-frequency analyses, we confirmed the dominance of a 5-6 Hz theta activity in right and of a low-gamma (25-45 Hz) activity in left primary auditory cortices (A1/A2), during both resting state and syllable processing. We further detected high-theta (7-8 Hz) resting activity in left primary, but also associative auditory regions. In left BA22, its phase correlated with high-gamma induced power. Such a hierarchical relationship across theta and gamma frequency bands (theta/gamma phase-amplitude coupling) could index the process by which the neural code shifts from stimulus feature- to phonological- encoding, and is associated with the transition from evoked to induced power responses. These data suggest that theta and gamma activity in right and left auditory cortices bear different functions. They support a scheme where slow parsing of the acoustic information dominates in right-hemisphere at a syllabic (5-6 Hz) rate, and left auditory cortex exhibits a more complex cascade of oscillations, reflecting the possible extraction of transient acoustic cues at a fast (~25-45 Hz) rate, subsequently integrated at a slower, e.g. syllabic one. Slow oscillations could functionally participate to speech processing by structuring gamma activity in left BA22, where abstract percepts emerge.

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.

Investigating cognitive brain functions using non-invasive electrophysiology can be challenging due to the particularities of the task-related EEG activity, the depth of the activated brain areas, and the extent of the networks involved. Stereoelectroencephalographic (SEEG) investigations in patients with drug-resistant epilepsy offer an extraordinary opportunity to validate information derived from non-invasive recordings at macro-scales. The SEEG approach can provide brain activity with high spatial specificity during tasks that target specific cognitive processes (e.g., memory). Full validation is possible only when performing simultaneous scalp SEEG recordings, which allows recording signals in the exact same brain state. This is the approach we have taken in 12 subjects performing a visual memory task that requires the recognition of previously viewed objects. The intracranial signals on 965 contact pairs have been compared to 391 simultaneously recorded scalp signals at a regional and whole-brain level, using multivariate pattern analysis. The results show that the task conditions are best captured by intracranial sensors, despite the limited spatial coverage of SEEG electrodes, compared to the whole-brain non-invasive recordings. Applying beamformer source reconstruction or independent component analysis does not result in an improvement of the multivariate task decoding performance using surface sensor data. By analyzing a joint scalp and SEEG dataset, we investigated whether the two types of signals carry complementary information that might improve the machine-learning classifier performance. This joint analysis revealed that the results are driven by the modality exhibiting best individual performance, namely SEEG.

Stereo-electroencephalography (SEEG) is the surgical implantation of electrodes in the brain to better localize the epileptic network in pharmaco-resistant epileptic patients. This technique has exquisite spatial and temporal resolution. Still, the number and the position of the electrodes in the brain is limited and determined by the semiology and/or preliminary non-invasive examinations, leading to a large number of unexplored brain structures in each patient. Here, we propose a new approach to reconstruct the activity of non-sampled structures in SEEG, based on independent component analysis (ICA) and dipole source localization. We have tested this approach with an auditory stimulation dataset in ten patients. The activity directly recorded from the auditory cortex served as ground truth and was compared to the ICA applied on all non-auditory electrodes. Our results show that the activity from the auditory cortex can be reconstructed at the single trial level from contacts as far as ∼40 mm from the source. Importantly, this reconstructed activity is localized via dipole fitting in the proximity of the original source. In addition, we show that the size of the confidence interval of the dipole fitting is a good indicator of the reliability of the result, which depends on the geometry of the SEEG implantation. Overall, our approach allows reconstructing the activity of structures far from the electrode locations, partially overcoming the spatial sampling limitation of intracerebral recordings.

Magnetoencephalography (MEG) is a powerful tool for estimating brain connectivity with both good spatial and temporal resolution. It is particularly helpful in epilepsy to characterize non-invasively the epileptic networks. However, using MEG to map brain networks requires solving a difficult inverse problem that introduces uncertainty in the activity localization and connectivity measures. Our goal here was to compare independent component analysis (ICA) followed by dipole source localization and the linearly constrained minimum-variance beamformer (LCMV-BF) for characterizing regions with interictal epileptic activity and their dynamic connectivity. After a simulation study, we compared ICA and LCMV-BF results with intracerebral EEG (stereotaxic EEG, SEEG) recorded simultaneously in 8 epileptic patients, which provide a unique ‘ground truth’ to which non-invasive results can be confronted. We compared the signal time courses extracted applying ICA and LCMV-BF on MEG data to that of SEEG, both for the actual signals and the dynamic connectivity computed using cross-correlation (evolution of links in time).With our simulations, we illustrated the different effect of the temporal and spatial correlation among sources on the two methods. While ICA was more affected by the temporal correlation but robust against spatial configurations, LCMV-BF showed opposite behavior. Moreover, ICA seems more suited to retrieve the simulated networks.In case of real patient data, good MEG/SEEG correlation and good localization were obtained in 6 out of 8 patients. In 4 of them ICA had the best performance (higher correlation, lower localization distance). In terms of dynamic connectivity, the evolution in time of the cross-correlation links could be retrieved in 5 patients out of 6, however, with more variable results in terms of correlation and distance. In two patients LCMV-BF had better results than ICA. In one patient the two methods showed equally good outcomes, and in the remaining two patients ICA performed best.In conclusion, our results obtained by exploiting simultaneous MEG/SEEG recordings suggest that ICA and LCMV-BF have complementary qualities for retrieving the dynamics of interictal sources and their network interactions.