Systematic review of seizure-onset patterns in stereo-electroencephalography: Current state and future directions.

OBJECTIVE: Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset. Specifically, SOPs with low-voltage fast activity (LVFA) are associated with seizure-free outcome (Engel I). However, several classifications and various terms corresponding to the same pattern have been reported, challenging its use in clinical practice. METHOD: Following the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guideline, we performed a systematic review of studies describing SOPs along with accompanying figures depicting the reported SOP in SEEG. RESULTS: Of 1799 studies, 22 met the selection criteria. Among the various SOPs, we observed that the terminology for low frequency periodic spikes exhibited the most variability, whereas LVFA is the most frequently used term of this pattern. Some SOP terms were inconsistent with standard EEG terminology. Finally, there was a significant but weak association between presence of LVFA and seizure-free outcome. CONCLUSION: Divergent terms were used to describe the same SOPs and some of these terms showed inconsistencies with the standard EEG terminology. Additionally, our results confirmed the link between patterns with LVFA and seizure-free outcomes. However, this association was not strong. SIGNIFICANCE: These results underline the need for standardization of SEEG terminology.

Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical-imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency, and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and inter-individual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Differential relational memory impairment in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory, including episodic, semantic, and spatial memory processes. While it is widely accepted that TLE-associated hippocampal alterations underlie memory deficits, it remains unclear whether impairments relate to a specific cognitive domain or multiple ones. METHODS: We administered a recently validated task paradigm to evaluate episodic, semantic, and spatial memory in 24 pharmacoresistant TLE patients and 50 age- and sex-matched healthy controls. We carried out two-way analyses of variance to identify memory deficits in individuals with TLE relative to controls across different relational memory domains, and used partial least squares correlation to identify factors contributing to variations in relational memory performance across both cohorts. RESULTS: Compared to controls, TLE patients showed marked impairments in episodic and spatial memory, with mixed findings in semantic memory. Even when additionally controlling for age, sex, and overall cognitive function, between-group differences persisted along episodic and spatial domains. Moreover, age, diagnostic group, and hippocampal volume were all associated with relational memory behavioral phenotypes. SIGNIFICANCE: Our behavioral findings show graded deficits across relational memory domains in people with TLE, which provides further insights into the complex pattern of cognitive impairment in the condition.

Timing matters for accurate identification of the epileptogenic zone.

OBJECTIVE: Interictal biomarkers of the epileptogenic zone (EZ) and their use in machine learning models open promising avenues for improvement of epilepsy surgery evaluation. Currently, most studies restrict their analysis to short segments of intracranial EEG (iEEG). METHODS: We used 2381 hours of iEEG data from 25 patients to systematically select 5-minute segments across various interictal conditions. Then, we tested machine learning models for EZ localization using iEEG features calculated within these individual segments or across them and evaluated the performance by the area under the precision-recall curve (PRAUC). RESULTS: On average, models achieved a score of 0.421 (the result of the chance classifier was 0.062). However, the PRAUC varied significantly across the segments (0.323-0.493). Overall, NREM sleep achieved the highest scores, with the best results of 0.493 in N2. When using data from all segments, the model performed significantly better than single segments, except NREM sleep segments. CONCLUSIONS: The model based on a short segment of iEEG recording can achieve similar results as a model based on prolonged recordings. The analyzed segment should, however, be carefully and systematically selected, preferably from NREM sleep. SIGNIFICANCE: Random selection of short iEEG segments may give rise to inaccurate localization of the EZ.

Intracerebral Dynamics of Sleep Arousals: A Combined Scalp-Intracranial EEG Study.

As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and are important for sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals during nonrapid eye movement sleep into slow wave (SW) and non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions (p < 0.05; d = 0.06-0.63), while gamma and high-frequency (HF) activities decreased in up to 18 regions across the five brain lobes (p < 0.05; d = 0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals (p < 0.05 in 22 regions; d = 0.10-0.39), while it widely decreased during non-SW arousals (p < 0.05 in 19 regions; d = 0.10-0.30). Despite these main patterns, unique activities were observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals.

Spike ripples localize the epileptogenic zone best: an international intracranial study.

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone (EZ) compared to other leading interictal biomarkers in a multicenter, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centers who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection (ILAE 1 outcome) and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001, P < 0.001). Among ILAE 1 subjects, the mean spike ripple rate was higher in the RV (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared to ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01), or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicenter cohort, when surgical resection was successful, the majority of spike ripples were removed. Further, automatically detected spike ripples have improved specificity for epileptogenic tissue compared to spikes, spike-gamma, wideband HFOs, ripples, and fast ripples.

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

Recent advances in clinical electroencephalography.

PURPOSE OF REVIEW: Clinical electroencephalography (EEG) is a conservative medical field. This explains likely the significant gap between clinical practice and new research developments. This narrative review discusses possible causes of this discrepancy and how to circumvent them. More specifically, we summarize recent advances in three applications of clinical EEG: source imaging (ESI), high-frequency oscillations (HFOs) and EEG in critically ill patients. RECENT FINDINGS: Recently published studies on ESI provide further evidence for the accuracy and clinical utility of this method in the multimodal presurgical evaluation of patients with drug-resistant focal epilepsy, and opened new possibilities for further improvement of the accuracy. HFOs have received much attention as a novel biomarker in epilepsy. However, recent studies questioned their clinical utility at the level of individual patients. We discuss the impediments, show up possible solutions and highlight the perspectives of future research in this field. EEG in the ICU has been one of the major driving forces in the development of clinical EEG. We review the achievements and the limitations in this field. SUMMARY: This review will promote clinical implementation of recent advances in EEG, in the fields of ESI, HFOs and EEG in the intensive care.

Consistency of electrical source imaging in presurgical evaluation of epilepsy across different vigilance states.

OBJECTIVE: The use of electrical source imaging (ESI) in assessing the source of interictal epileptic discharges (IEDs) is gaining increasing popularity in presurgical work-up of patients with drug-resistant focal epilepsy. While vigilance affects the ability to locate IEDs and identify the epileptogenic zone, we know little about its impact on ESI. METHODS: We studied overnight high-density electroencephalography recordings in focal drug-resistant epilepsy. IEDs were marked visually in each vigilance state, and examined in the sensor and source space. ESIs were calculated and compared between all vigilance states and the clinical ground truth. Two conditions were considered within each vigilance state, an unequalized and an equalized number of IEDs. RESULTS: The number, amplitude, and duration of IEDs were affected by the vigilance state, with N3 sleep presenting the highest number, amplitude, and duration for both conditions (P < 0.001), while signal-to-noise ratio only differed in the unequalized condition (P < 0.001). The vigilance state did not affect channel involvement (P > 0.05). ESI maps showed no differences in distance, quality, extent, or maxima distances compared to the clinical ground truth for both conditions (P > 0.05). Only when an absolute reference (wakefulness) was used, the channel involvement (P < 0.05) and ESI source extent (P < 0.01) were impacted during rapid-eye-movement (REM) sleep. Clustering of amplitude-sensitive and -insensitive ESI maps pointed to amplitude rather than the spatial profile as the driver (P < 0.05). INTERPRETATION: IED ESI results are stable across vigilance states, including REM sleep, if controlled for amplitude and IED number. ESI is thus stable and invariant to the vigilance state.

Scalp and hippocampal sleep correlates of memory function in drug-resistant temporal lobe epilepsy.

Seminal animal studies demonstrated the role of sleep oscillations such as cortical slow waves, thalamocortical spindles, and hippocampal ripples in memory consolidation. In humans, whether ripples are involved in sleep-related memory processes is less clear. Here, we explored the interactions between sleep oscillations (measured as traits) and general episodic memory abilities in 26 adults with drug-resistant temporal lobe epilepsy who performed scalp-intracranial electroencephalographic recordings and neuropsychological testing, including two analogous hippocampal-dependent verbal and nonverbal memory tasks. We explored the relationships between hemispheric scalp (spindles, slow waves) and hippocampal physiological and pathological oscillations (spindles, slow waves, ripples, and epileptic spikes) and material-specific memory function. To differentiate physiological from pathological ripples, we used multiple unbiased data-driven clustering approaches. At the individual level, we found material-specific cerebral lateralization effects (left-verbal memory, right-nonverbal memory) for all scalp spindles (rs > 0.51, ps < 0.01) and fast spindles (rs > 0.61, ps < 0.002). Hippocampal epileptic spikes and short pathological ripples, but not physiological oscillations, were negatively (rs > -0.59, ps < 0.01) associated with verbal learning and retention scores, with left lateralizing and antero-posterior effects. However, data-driven clustering failed to separate the ripple events into defined clusters. Correlation analyses with the resulting clusters revealed no meaningful or significant associations with the memory scores. Our results corroborate the role of scalp spindles in memory processes in patients with drug-resistant temporal lobe epilepsy. Yet, physiological and pathological ripples were not separable when using data-driven clustering, and thus our findings do not provide support for a role of sleep ripples as trait-like characteristics of general memory abilities in epilepsy.

The Differing Effects of Sleep on Ictal and Interictal Network Dynamics in Drug-Resistant Epilepsy.

OBJECTIVE: Sleep has important influences on focal interictal epileptiform discharges (IEDs), and the rates and spatial extent of IEDs are increased in non-rapid eye movement (NREM) sleep. In contrast, the influence of sleep on seizures is less clear, and its effects on seizure topography are poorly documented. We evaluated the influences of NREM sleep on ictal spatiotemporal dynamics and contrasted these with interictal network dynamics. METHODS: We included patients with drug-resistant focal epilepsy who underwent continuous intracranial electroencephalography (iEEG) with depth electrodes. Patients were selected if they had 1 to 3 seizures from each vigilance state, wakefulness and NREM sleep, within a 48-hour window, and under the same antiseizure medication. A 10-minute epoch of the interictal iEEG was selected per state, and IEDs were detected automatically. A total of 25 patients (13 women; aged 32.5 ± 7.1 years) were included. RESULTS: The seizure onset pattern, duration, spatiotemporal propagation, and latency of ictal high-frequency activity did not differ significantly between wakefulness and NREM sleep (all p > 0.05). In contrast, IED rates and spatial distribution were increased in NREM compared with wakefulness (p < 0.001, Cliff's d = 0.48 and 0.49). The spatial overlap between vigilance states was higher for seizures (57.1 ± 40.1%) than IEDs (41.7 ± 46.2%; p = 0.001, Cliff's d = 0.51). INTERPRETATION: In contrast to its effects on IEDs, NREM sleep does not affect ictal spatiotemporal dynamics. This suggests that once the brain surpasses the seizure threshold, it will follow the underlying epileptic network irrespective of the vigilance state. These findings offer valuable insights into neural network dynamics in epilepsy and have important clinical implications for localizing seizure foci. ANN NEUROL 2023.

Rapid eye movement sleep affects interictal epileptic activity differently in mesiotemporal and neocortical areas.

OBJECTIVE: Rapid eye movement (REM) sleep reduces the rate and extent of interictal epileptiform discharges (IEDs). Breakthrough epileptic activity during REM sleep is therefore thought to best localize the seizure onset zone (SOZ). We utilized polysomnography combined with direct cortical recordings to investigate the influences of anatomical locations and the time of night on the suppressive effect of REM sleep on IEDs. METHODS: Forty consecutive patients with drug-resistant focal epilepsy underwent combined polysomnography and stereo-electroencephalography during presurgical evaluation. Ten-minute interictal epochs were selected 2 h prior to sleep onset (wakefulness), and from the first and second half of the night during non-REM (NREM) sleep and REM sleep. IEDs were detected automatically across all channels. Anatomic localization, time of night, and channel type (within or outside the SOZ) were tested as modulating factors. RESULTS: Relative to wakefulness, there was a suppression of IEDs by REM sleep in neocortical regions (median = -27.6%), whereas mesiotemporal regions showed an increase in IEDs (19.1%, p = .01, d = .39). This effect was reversed when comparing the regional suppression of IEDs by REM sleep relative to NREM sleep (-35.1% in neocortical, -58.7% in mesiotemporal, p < .001, d = .39). Across all patients, no clinically relevant novel IED regions were observed in REM sleep versus NREM or wakefulness based on our predetermined thresholds (4 IEDs/min in REM, 0 IEDs/min in NREM and wakefulness). Finally, there was a reduction in IEDs in late (NREM: 1.08/min, REM: .61/min) compared to early sleep (NREM: 1.22/min, REM: .69/min) for both NREM (p < .001, d = .21) and REM (p = .04, d = .14). SIGNIFICANCE: Our results demonstrate a spatiotemporal effect of IED suppression by REM sleep relative to wakefulness in neocortical but not mesiotemporal regions, and in late versus early sleep. This suggests the importance of considering sleep stage interactions and the potential influences of anatomical locations when using IEDs to define the epileptic focus.

Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies.

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common pharmaco-resistant epilepsies in adults. While hippocampal pathology is the hallmark of this condition, emerging evidence indicates that brain alterations extend beyond the mesiotemporal epicenter and affect macroscale brain function and cognition. We studied macroscale functional reorganization in TLE, explored structural substrates, and examined cognitive associations. We investigated a multisite cohort of 95 patients with pharmaco-resistant TLE and 95 healthy controls using state-of-the-art multimodal 3T magnetic resonance imaging (MRI). We quantified macroscale functional topographic organization using connectome dimensionality reduction techniques and estimated directional functional flow using generative models of effective connectivity. We observed atypical functional topographies in patients with TLE relative to controls, manifesting as reduced functional differentiation between sensory/motor networks and transmodal systems such as the default mode network, with peak alterations in bilateral temporal and ventromedial prefrontal cortices. TLE-related topographic changes were consistent in all three included sites and reflected reductions in hierarchical flow patterns between cortical systems. Integration of parallel multimodal MRI data indicated that these findings were independent of TLE-related cortical grey matter atrophy, but mediated by microstructural alterations in the superficial white matter immediately beneath the cortex. The magnitude of functional perturbations was robustly associated with behavioral markers of memory function. Overall, this work provides converging evidence for macroscale functional imbalances, contributing microstructural alterations, and their associations with cognitive dysfunction in TLE.

Regional variability in intracerebral properties of NREM to REM sleep transitions in humans.

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

Validating MEG source imaging of resting state oscillatory patterns with an intracranial EEG atlas.

BACKGROUND: Magnetoencephalography (MEG) is a widely used non-invasive tool to estimate brain activity with high temporal resolution. However, due to the ill-posed nature of the MEG source imaging (MSI) problem, the ability of MSI to identify accurately underlying brain sources along the cortical surface is still uncertain and requires validation. METHOD: We validated the ability of MSI to estimate the background resting state activity of 45 healthy participants by comparing it to the intracranial EEG (iEEG) atlas (https://mni-open-ieegatlas. RESEARCH: mcgill.ca/). First, we applied wavelet-based Maximum Entropy on the Mean (wMEM) as an MSI technique. Next, we converted MEG source maps into intracranial space by applying a forward model to the MEG-reconstructed source maps, and estimated virtual iEEG (ViEEG) potentials on each iEEG channel location; we finally quantitatively compared those with actual iEEG signals from the atlas for 38 regions of interest in the canonical frequency bands. RESULTS: The MEG spectra were more accurately estimated in the lateral regions compared to the medial regions. The regions with higher amplitude in the ViEEG than in the iEEG were more accurately recovered. In the deep regions, MEG-estimated amplitudes were largely underestimated and the spectra were poorly recovered. Overall, our wMEM results were similar to those obtained with minimum norm or beamformer source localization. Moreover, the MEG largely overestimated oscillatory peaks in the alpha band, especially in the anterior and deep regions. This is possibly due to higher phase synchronization of alpha oscillations over extended regions, exceeding the spatial sensitivity of iEEG but detected by MEG. Importantly, we found that MEG-estimated spectra were more comparable to spectra from the iEEG atlas after the aperiodic components were removed. CONCLUSION: This study identifies brain regions and frequencies for which MEG source analysis is likely to be reliable, a promising step towards resolving the uncertainty in recovering intracerebral activity from non-invasive MEG studies.

Stimulation to probe, excite, and inhibit the epileptic brain.

Direct cortical stimulation has been applied in epilepsy for nearly a century and has experienced a renaissance, given unprecedented opportunities to probe, excite, and inhibit the human brain. Evidence suggests stimulation can increase diagnostic and therapeutic utility in patients with drug-resistant epilepsies. However, choosing appropriate stimulation parameters is not a trivial issue, and is further complicated by epilepsy being characterized by complex brain state dynamics. In this article derived from discussions at the ICTALS 2022 Conference (International Conference on Technology and Analysis for Seizures), we succinctly review the literature on cortical stimulation applied acutely and chronically to the epileptic brain for localization, monitoring, and therapeutic purposes. In particular, we discuss how stimulation is used to probe brain excitability, discuss evidence on the usefulness of stimulation to trigger and stop seizures, review therapeutic applications of stimulation, and finally discuss how stimulation parameters are impacted by brain dynamics. Although research has advanced considerably over the past decade, there are still significant hurdles to optimizing use of this technique. For example, it remains unclear to what extent short timescale diagnostic biomarkers can predict long-term outcomes and to what extent these biomarkers add information to already existing biomarkers from passive electroencephalographic recordings. Further questions include the extent to which closed loop stimulation offers advantages over open loop stimulation, what the optimal closed loop timescales may be, and whether biomarker-informed stimulation can lead to seizure freedom. The ultimate goal of bioelectronic medicine remains not just to stop seizures but rather to cure epilepsy and its comorbidities.

SEEGAtlas: A framework for the identification and classification of depth electrodes using clinical images.

Objective.Accurate localization, classification, and visualization of intracranial electrodes are fundamental for analyzing intracranial electrographic recordings. While manual contact localization is the most common approach, it is time-consuming, prone to errors, and is particularly challenging and subjective in low quality images, which are common in clinical practice. Automatically locating and interactively visualizing where each of the 100-200 individual contacts records in the brain is essential for understanding the neural origins of intracranial EEG.Approach.We introduced the SEEGAtlas plugin for the IBIS system, an open-source software platform for image-guided neurosurgery and multi-modal image visualization. SEEGAtlas extends IBIS functionalities to semi-automatically locate depth-electrode contact coordinates and automatically label the tissue type and anatomical region in which each contact is located. To illustrate the capabilities of SEEGAtlas and to validate the algorithms, clinical magnetic resonance images (MRIs) before and after electrode implantation of ten patients with depth electrodes implanted to localize the origin of their epileptic seizures were analyzed.Main Results. Visually identified contact coordinates were compared with the coordinates obtained by SEEGAtlas, resulting in a median difference of 1.4 mm. The agreement was lower for MRIs with weak susceptibility artifacts than for high-quality images. The tissue type was classified with 86% agreement with visual inspection. The anatomical region was classified as having a median agreement across patients of 82%.Significance. The SEEGAtlas plugin is user-friendly and enables accurate localization and anatomical labeling of individual contacts along implanted electrodes, together with powerful visualization tools. Employing the open-source SEEGAtlas results in accurate analysis of the recorded intracranial electroencephalography (EEG), even when only suboptimal clinical imaging is available. A better understanding of the cortical origin of intracranial EEG would help improve clinical interpretation and answer fundamental questions of human neuroscience.