Net synaptic drive of fast-spiking interneurons is inverted towards inhibition in human FCD I epilepsy.

Focal cortical dysplasia type I (FCD I) is the most common cause of pharmaco-resistant epilepsy with the poorest prognosis. To understand the epileptogenic mechanisms of FCD I, we obtained tissue resected from patients with FCD I epilepsy, and from tumor patients as control. Using whole-cell patch clamp in acute human brain slices, we investigated the cellular properties of fast-spiking interneurons (FSINs) and pyramidal neurons (PNs) within the ictal onset zone. In FCD I epilepsy, FSINs exhibited lower firing rates from slower repolarization and action potential broadening, while PNs had increased firing. Importantly, excitatory synaptic drive of FSINs increased progressively with the scale of cortical activation as a general property across species, but this relationship was inverted towards net inhibition in FCD I epilepsy. Further comparison with intracranial electroencephalography (iEEG) from the same patients revealed that the spatial extent of pathological high-frequency oscillations (pHFO) was associated with synaptic events at FSINs.

Origami-inspired soft fluidic actuation for minimally invasive large-area electrocorticography.

Electrocorticography is an established neural interfacing technique wherein an array of electrodes enables large-area recording from the cortical surface. Electrocorticography is commonly used for seizure mapping however the implantation of large-area electrocorticography arrays is a highly invasive procedure, requiring a craniotomy larger than the implant area to place the device. In this work, flexible thin-film electrode arrays are combined with concepts from soft robotics, to realize a large-area electrocorticography device that can change shape via integrated fluidic actuators. We show that the 32-electrode device can be packaged using origami-inspired folding into a compressed state and implanted through a small burr-hole craniotomy, then expanded on the surface of the brain for large-area cortical coverage. The implantation, expansion, and recording functionality of the device is confirmed in-vitro and in porcine in-vivo models. The integration of shape actuation into neural implants provides a clinically viable pathway to realize large-area neural interfaces via minimally invasive surgical techniques.

Gamma amplitude-envelope correlations are strongly elevated within hyperexcitable networks in focal epilepsy.

Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40-200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores > 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy.

Predictors of SOZ localization, subsequent surgical intervention, and seizure outcomes in iEEG.

OBJECTIVE: A third of the patients who undergo intracranial EEG (iEEG) for seizure-onset zone (SOZ) localization do not proceed to resective surgery for epilepsy, and over half of those who do continue to have seizures following treatment. To better identify candidates who are more likely to see benefits from undergoing iEEG, we investigated preoperative and iEEG peri-operative features associated with the localization of a putative SOZ, undergoing subsequent surgical treatment, and seizure outcomes. METHODS: We conducted a retrospective cohort study of consecutive patients who underwent iEEG from 2001 to 2022 at two institutions. Outcomes included SOZ identification, proceeding to surgical treatment (resection vs. neuromodulation), and subsequent seizure freedom. RESULTS: We identified 329 unique patients who were followed for a median of 3.9 (IQR:7) years, with a minimum of 2-year follow-up for seizure outcomes analyses. Multivariate analysis identified lateralized and lobar localization on scalp EEG (OR 3.8, p = 0.001) to be associated with SOZ localization. Patients with unilateral localization on scalp EEG (OR 3.0, p = 0.003), unilateral preimplantation hypothesis (OR 3.1, p = 0.001), and lesional preoperative MRI (OR 2.1, p = 0.033) were more likely to undergo resection than neuromodulation. Similarly, a unilateral pre-implantation hypothesis (OR 2.6, p < 0.001) favored seizure freedom, whereas prior neuromodulation (OR 0.3, p = 0.013) decreased the odds. Larger number of preoperative anti-seizure medications (ASMs) did not influence seizure freedom rates but did decrease favorable (Engel I, II) seizure outcomes (OR 0.7, p = 0.026). INTERPRETATION: Non-invasive localization data prior to iEEG are associated with subsequent resection and seizure freedom, independent of iEEG localization. Factors predictive of SOZ localization are not necessarily predictive of post-operative seizure freedom.

Voxeloc: A time-saving graphical user interface for localizing and visualizing stereo-EEG electrodes.

BACKGROUND: Thanks to its unrivalled spatial and temporal resolutions and signal-to-noise ratio, intracranial EEG (iEEG) is becoming a valuable tool in neuroscience research. To attribute functional properties to cortical tissue, it is paramount to be able to determine precisely the localization of each electrode with respect to a patient's brain anatomy. Several software packages or pipelines offer the possibility to localize manually or semi-automatically iEEG electrodes. However, their reliability and ease of use may leave to be desired. NEW METHOD: Voxeloc (voxel electrode locator) is a Matlab-based graphical user interface to localize and visualize stereo-EEG electrodes. Voxeloc adopts a semi-automated approach to determine the coordinates of each electrode contact, the user only needing to indicate the deep-most contact of each electrode shaft and another point more proximally. RESULTS: With a deliberately streamlined functionality and intuitive graphical user interface, the main advantages of Voxeloc are ease of use and inter-user reliability. Additionally, oblique slices along the shaft of each electrode can be generated to facilitate the precise localization of each contact. Voxeloc is open-source software and is compatible with the open iEEG-BIDS (Brain Imaging Data Structure) format. COMPARISON WITH EXISTING METHODS: Localizing full patients' iEEG implants was faster using Voxeloc than two comparable software packages, and the inter-user agreement was better. CONCLUSIONS: Voxeloc offers an easy-to-use and reliable tool to localize and visualize stereo-EEG electrodes. This will contribute to democratizing neuroscience research using iEEG.

Seizure Outcome After Intraoperative Electrocorticography-Tailored Epilepsy Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome. METHODS: PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; p < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; p < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87). DISCUSSION: Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

Spatial and temporal properties of intra-operatively recorded spikes and high frequency oscillations in focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasias (FCD) are characterized by distinct interictal spike patterns and high frequency oscillations (HFOs; ripples: 80-250 Hz; fast ripples: 250-500 Hz) in the intra-operative electrocorticogram (ioECoG). We studied the temporal relation between intra-operative spikes and HFOs and their relation to resected tissue in people with FCD with a favorable outcome. METHODS: We included patients who underwent ioECoG-tailored epilepsy surgery with pathology confirmed FCD and long-term Engel 1A outcome. Spikes and HFOs were automatically detected and visually checked in 1-minute pre-resection-ioECoG. Channels covering resected and non-resected tissue were compared using a logistic mixed model, assessing event numbers, co-occurrence ratios, and time-based properties. RESULTS: We found pre-resection spikes, ripples in respectively 21 and 20 out of 22 patients. Channels covering resected tissue showed high numbers of spikes and HFOs, and high ratios of co-occurring events. Spikes, especially with ripples, have a relatively sharp rising flank with a long descending flank and early ripple onset over resected tissue. CONCLUSIONS: A combined analysis of event numbers, ratios, and temporal relationships between spikes and HFOs may aid identifying epileptic tissue in epilepsy surgery. SIGNIFICANCE: This study shows a promising method for clinically relevant properties of events, closely associated with FCD.

An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Psychiatric complications following SEEG-guided radiofrequency thermocoagulations in patients with drug-resistant epilepsy.

SEEG-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic regions is a therapeutic option for patients with drug-resistant focal epilepsy who may have or not indication for epilepsy surgery. The most common adverse events of RF-TC are seizures, headaches, somatic pain, and sensory-motor deficits. If RF-TC could lead to psychiatric complications is unknown. In the present study, seven out of 164 patients (4.2 %) experienced psychiatric decompensation with or without memory deterioration after RF-TC of bilateral or unilateral amygdala and hippocampus. The appearance of symptoms was either acute, subacute, or chronic and the symptoms were either transient or lasted for several months. Common features among these patients were female sex, mesial temporal epilepsy, and a pre-existing history of psychological distress and memory dysfunction. Our study highlights the possibility of neuropsychiatric deterioration in specific patients following SEEG-guided RF-TC, despite its rarity.

Evaluation of Utility of Invasive Electroencephalography for Definitive Surgery in Patients with Drug-Resistant Epilepsy: A Systematic Review and Meta-Analysis.

When noninvasive tests are unable to define the epileptogenic zone in patients, intracranial electroencephalography (iEEG) is a method of localizing the epileptogenic zone. Compared with noninvasive evaluations, it offers more precise information about patterns of epileptiform activity, which results in useful diagnostic information that supports surgical decision-making. The primary aim of the present study was to assess the utility of iEEG for definitive surgery for patients with drug-resistant epilepsy. Online databases such as PubMed, Medline, Embase, Scopus, Cochrane Library, Web of Science, and IEEE Xplore were searched for MeSH terms and free-text keywords. The ROBINS I (risk of bias in non-randomized studies - of interventions) critical appraisal tool was used for quality assessment. The prevalence from different studies was pooled together using the inverse variance heterogeneity method. Egger's regression analysis and funnel plot were used to evaluate publication bias. The systematic review included 18 studies, and the meta-analysis included 10 studies to estimate the prevalence of seizure freedom (Engel class I) in patients undergoing surgery after iEEG. A total of 526 patients were included in the meta-analysis. The follow-up period ranged from 1 to 10 years. The overall pooled estimate of the prevalence of seizure freedom (Engel class I) for patients undergoing surgery after iEEG was 53% (95% confidence interval, 44%-62%). The results additionally demonstrated that 12 studies had a moderate risk of bias and 6 had a low risk. Future studies are crucial to enhance our understanding of iEEG to guide patient choices and unravel their implications.

Ictal fast activity chirps as markers of the epileptogenic zone.

The identification of the epileptogenic zone (EZ) boundaries is crucial for effective focal epilepsy surgery. We verify the value of a neurophysiological biomarker of focal ictogenesis, characterized by a low-voltage fast-activity ictal pattern (chirp) recorded with intracerebral electrodes during invasive presurgical monitoring (stereoelectroencephalography [SEEG]). The frequency content of SEEG signals was retrospectively analyzed with semiautomatic software in 176 consecutive patients with focal epilepsies that either were cryptogenic or presented with discordant anatomoelectroclinical findings. Fast activity seizure patterns with the spectrographic features of chirps were confirmed by computer-assisted analysis in 95.4% of patients who presented with heterogeneous etiologies and diverse lobar location of the EZ. Statistical analysis demonstrated (1) correlation between seizure outcome and concordance of sublobar regions included in the EZ defined by visual analysis and chirp-generating regions, (2) high concordance in contact-by contact analysis of 68 patients with Engel class Ia outcome, and (3) that discordance between chirp location and the visually outlined EZ correlated with worse seizure outcome. Seizure outcome analysis confirms the fast activity chirp pattern is a reproducible biomarker of the EZ in a heterogeneous group of patients undergoing SEEG.

Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups. METHODS: We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology. RESULTS: Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, p < 0.001; ripples 4.04, 2.32-7.04, p < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, p = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions (p = 0.02 after multiple correction). DISCUSSION: Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.

High-performance prediction of epilepsy surgical outcomes based on the genetic neural networks and hybrid iEEG marker.

Accurately identification of the seizure onset zone (SOZ) is pivotal for successful surgery in patients with medically refractory epilepsy. The purpose of this study is to improve the performance of model predicting the epilepsy surgery outcomes using genetic neural network (GNN) model based on a hybrid intracranial electroencephalography (iEEG) marker. We extracted 21 SOZ related markers based on iEEG data from 79 epilepsy patients. The least absolute shrinkage and selection operator (LASSO) regression was employed to integrated seven markers, selected after testing in pairs with all 21 biomarkers and 7 machine learning models, into a hybrid marker. Based on the hybrid marker, we devised a GNN model and compared its predictive performance for surgical outcomes with six other mainstream machine-learning models. Compared to the mainstream models, underpinning the GNN with the hybrid iEEG marker resulted in a better prediction of surgical outcomes, showing a significant increase of the prediction accuracy from approximately 87% to 94.3% (P = 0.0412). This study suggests that the hybrid iEEG marker can improve the performance of model predicting the epilepsy surgical outcomes, and validates the effectiveness of the GNN in characterizing and analyzing complex relationships between clinical data variables.

Generalisability of epileptiform patterns across time and patients.

The complexity of localising the epileptogenic zone (EZ) contributes to surgical resection failures in achieving seizure freedom. The distinct patterns of epileptiform activity during interictal and ictal phases, varying across patients, often lead to suboptimal localisation using electroencephalography (EEG) features. We posed two key questions: whether neural signals reflecting epileptogenicity generalise from interictal to ictal time windows within each patient, and whether epileptiform patterns generalise across patients. Utilising an intracranial EEG dataset from 55 patients, we extracted a large battery of simple to complex features from stereo-EEG (SEEG) and electrocorticographic (ECoG) neural signals during interictal and ictal windows. Our features (n = 34) quantified many aspects of the signals including statistical moments, complexities, frequency-domain and cross-channel network attributes. Decision tree classifiers were then trained and tested on distinct time windows and patients to evaluate the generalisability of epileptogenic patterns across time and patients, respectively. Evidence strongly supported generalisability from interictal to ictal time windows across patients, particularly in signal power and high-frequency network-based features. Consistent patterns of epileptogenicity were observed across time windows within most patients, and signal features of epileptogenic regions generalised across patients, with higher generalisability in the ictal window. Signal complexity features were particularly contributory in cross-patient generalisation across patients. These findings offer insights into generalisable features of epileptic neural activity across time and patients, with implications for future automated approaches to supplement other EZ localisation methods.

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.

Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

The effect of propofol on effective brain networks.

OBJECTIVE: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. METHODS: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. RESULTS: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. CONCLUSIONS: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SIGNIFICANCE: The primary network topology is preserved under propofol.

Systematic 1 Hz direct electrical stimulation for seizure induction: A reliable method for localizing seizure onset zone and predicting seizure freedom.

OBJECTIVE: To prospectively investigate the utility of seizure induction using systematic 1 Hz stimulation by exploring its concordance with the spontaneous seizure onset zone (SOZ) and relation to surgical outcome; comparison with seizures induced by non-systematic 50 Hz stimulation was attempted as well. METHODS: Prospective cohort study from 2018 to 2021 with ≥ 1 y post-surgery follow up at Yale New Haven Hospital. With 1 Hz, all or most of the gray matter contacts were stimulated at 1, 5, and 10 mA for 30-60s. With 50 Hz, selected gray matter contacts outside of the medial temporal regions were stimulated at 1-5 mA for 0.5-3s. Stimulation was bipolar, biphasic with 0.3 ms pulse width. The Yale Brain Atlas was used for data visualization. Variables were analyzed using Fisher's exact, χ2, or Mann-Whitney test. RESULTS: Forty-one consecutive patients with refractory epilepsy undergoing intracranial EEG for localization of SOZ were included. Fifty-six percent (23/41) of patients undergoing 1 Hz stimulation had seizures induced, 83% (19/23) habitual (clinically and electrographically). Eighty two percent (23/28) of patients undergoing 50 Hz stimulation had seizures, 65% (15/23) habitual. Stimulation of medial temporal or insular regions with 1 Hz was more likely to induce seizures compared to other regions [15/32 (47%) vs. 2/41 (5%), p < 0.001]. Sixteen patients underwent resection; 11/16 were seizure free at one year and all 11 had habitual seizures induced by 1 Hz; 5/16 were not seizure free at one year and none of those 5 had seizures with 1 Hz (11/11 vs 0/5, p < 0.0001). No patients had convulsions with 1 Hz stimulation, but four did with 50 Hz (0/41 vs. 4/28, p = 0.02). SIGNIFICANCE: Induction of habitual seizures with 1 Hz stimulation can reliably identify the SOZ, correlates with excellent surgical outcome if that area is resected, and may be superior (and safer) than 50 Hz for this purpose. However, seizure induction with 1 Hz was infrequent outside of the medial temporal and insular regions in this study.

Patient experiences of resection versus responsive neurostimulation for drug-resistant epilepsy.

This study explored illness experiences and decision-making among patients with epilepsy who underwent two different types of surgical interventions: resection versus implantation of the NeuroPace Responsive Neurostimulation System (RNS). We recruited 31 participants from a level four epilepsy center in an academic medical institution. We observed 22 patient clinic visits (resection: n = 10, RNS: n = 12) and conducted 18 in-depth patient interviews (resection: n = seven, RNS: n = 11); most visits and interviews included patient caregivers. Using an applied ethnographic approach, we identified three major themes in the experiences of resection versus RNS patients. First, for patients in both cohorts, the therapeutic journey was circuitous in ways that defied standardized first-, second-, and third- line of care models. Second, in conceptualizing risk, resection patients emphasized the permanent loss of "taking out" brain tissue whereas RNS patients highlighted the reversibility of "putting in" a device. Lastly, in considering benefit, resection patients perceived their surgery as potentially curative while RNS patients understood implantation as primarily palliative with possible additional diagnostic benefit from chronic electrocorticography. Insight into the perspectives of patients and caregivers may help identify key topics for counseling and exploration by clinicians.