Balu Krishnan

Objective: Magnetoencephalography (MEG) is used widely in presurgical evaluation of medically intractable epilepsy. Prior research has documented the added value of MEG in refining surgical strategies; however, not all MEG clusters require resection for seizure freedom, suggesting that they represent nodes within a broader epileptic network, with differing importance for epileptogenic zone (EZ) localization. We examined whether MEG cluster characteristics can identify clusters most relevant to EZ. Methods: We studied 101 patients with focal epilepsy who underwent intracranial electroencephalography (ICEEG), resective surgery, and became seizure‐free at 1 year. MEG recordings were obtained with a 306‐channel system and analyzed using single equivalent current dipole (SECD) modeling. Clusters were categorized by anatomic location, tightness, and orientation and defined as “matched” with the EZ if ≥70% of dipoles were included in the resection. A sublobar anatomo‐functional scheme was used to map cluster–resection spatial relationships. Logistic regression and generalized linear mixed models with patient as a random effect evaluated age, sex, epilepsy duration, prior surgery, and cluster characteristics. Match rates were compared across pathology groups. Results: Clusters in frontal and interlobar junctional regions were less likely than temporal clusters to be matched ( p = .003 and p = .005). Clusters from patients with multiple clusters were less likely to be matched ( p < .001). Tight clusters were more likely matched than loose clusters ( p = .013). Cluster–resection mapping identified distinct propagation patterns, including anterior–posterior temporal and ipsilateral–contralateral opercular spread. Among 49 mismatched clusters sampled with ICEEG, 91% showed interictal discharges and 63% were involved in seizure propagation. Match rates did not differ by pathology. Significance: Our findings support incorporating detailed analysis of MEG cluster characteristics into presurgical evaluation to refine EZ localization, especially for invasive evaluation. Cluster–resection mapping patterns may assist surgical hypothesis generation. Matched clusters in mild malformation of cortical development and negative pathology cases further highlight MEG's value in challenging pathological substrates.

Accurate localization of the seizure onset zone (SOZ) is a central determinant of surgical outcome in drug-resistant focal epilepsy, yet identifying it from stereo-electroencephalography (SEEG) remains a slow, subjective visual task. We developed a self-supervised CNN--Transformer encoder (CSOPE-Net; Contrastive Seizure-Onset Pattern Encoder) that learns contact-level peri-ictal representations from 60-second superlet spectrograms through InfoNCE contrastive pretraining. We evaluated this representation as a framework for SOZ localization, seizure-onset phenotype clustering, and identification of clinically labeled non-SOZ contacts with SOZ-like morphology in poor-outcome patients. Across 149 patients partitioned a priori into a development cohort (n=119) and an independent held-out cohort (n=30; 18 good-outcome subjects for classification validation and 12 poor-outcome subjects for SOZ-proximal replication), the model achieved aggregate ROC-AUC 0.854 under leave-one-subject-out cross-validation, 0.935 on held-out good-outcome subjects, and 0.822 on an independent external cohort (HUP iEEG dataset), with consistent performance across patients. The learned representation organized seizure onsets into reproducible phenotype families and, in poor-outcome patients, flagged clinically labeled non-SOZ contacts whose spectrotemporal features resembled those of high-confidence SOZ contacts. This signal reproduced in held-out data, and in a blinded re-review three experts endorsed these contacts as showing ictal-onset morphology at approximately 15-fold higher odds than matched non-SOZ controls. This framework augments expert SEEG review and surfaces candidate contacts for re-review in poor-outcome cases.

Objective: Surgical decision‐making in temporal lobe epilepsy (TLE) faces a critical challenge in determining whether the hippocampus can be safely spared during anterior temporal resection, particularly when surgery involves the language‐dominant hemisphere. We investigated whether presurgical network control metrics derived from magnetoencephalography (MEG) can differentiate patients who achieved seizure freedom with hippocampal resection (HR) from those who achieved seizure freedom with hippocampal sparing (HS). Methods: We analyzed presurgical spike‐free interictal MEG in 25 TLE patients with seizure freedom after anterior temporal resection (19 with hippocampal resection, 6 with sparing). Functional networks constructed from MEG data were partitioned into communities using a Louvain‐based consensus clustering algorithm. Within identified hippocampal‐related communities from each patient, we applied control centrality analysis to quantify the influence of each node on community synchronizability. Group differences were assessed using Fisher’s exact tests with false discovery rate (FDR) correction applied within each frequency band and hemisphere. Leave‐one‐subject‐out (LOSO) sensitivity analysis assessed the robustness of findings to individual subjects. Results: After FDR correction, synchronization of the contralateral anterior superior temporal sulcus (STS) in the HS group at beta band emerged as the primary finding ( p = .001, q = .02). This finding showed 100% stability in LOSO and persisted in a subgroup analysis excluding patients with hippocampal seizure onset ( p = .004). At p < .05, additional region‐frequency differences formed a coherent anatomic pattern: the HR group showed higher synchronization fractions within ipsilateral limbic structures, whereas the HS group showed higher synchronization in the ipsilateral posterior hippocampus and contralateral temporal regions with 100% LOSO stability. Significance: Presurgical MEG‐based network control analysis identified contralateral anterior STS synchronization as a candidate biomarker for hippocampal sparing eligibility in TLE. This proof‐of‐concept finding warrants prospective validation as potential tools to support individualized surgical planning beyond localization‐based approaches.

Alexopoulos et al. consider whether adding thalamic electrodes during SEEG improves patient outcomes. They conclude that the evidence remains limited and heterogeneous, and recommend cautious use within ethically and methodologically rigorous trials until the benefits and risks have been more clearly established.

Objective . Epilepsy is characterized by dynamic disruptions in brain networks, yet the spatiotemporal organization of directional interactions underlying ictal transitions remains incompletely understood. This study investigates peri-ictal transition patterns in mesial temporal lobe epilepsy (MTLE) by characterizing directional connectivity dynamics from intracranial stereo-electroencephalography (SEEG) seizure recordings. Approach . We analyzed SEEG data from 10 patients with MTLE who subsequently achieved seizure freedom following surgical resection. We quantified directional connectivity using directed transfer function measures across preictal, ictal, and post-ictal phases. We then applied clustering analyses to identify reproducible dynamical connectivity patterns and evaluated their consistency across seizures and patients. Main results . We identified distinct out-degree connectivity patterns across seizure phases, each associated with specific anatomical regions. Regions corresponding to the epileptogenic zone exhibited elevated out-degree during the preictal and early ictal periods, whereas non-resected regions showed increased out-degree during ictal termination and postictal phases. These patterns remained consistent across patients and seizures, demonstrating a structured and phase-dependent organization of directional information flow during seizure evolution. Significance . This study identifies stereotypical and reproducible peri-ictal directional connectivity patterns in MTLE. By characterizing how information flow evolves across seizure phases, our findings advance network-level understanding of ictal transitions and provide a reproducible framework for future studies of seizure network dynamics.

Objective: Epilepsy surgery is an effective treatment option for patients with medically refractory epilepsy due to mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). The success of surgery depends on the accurate localization of the epileptogenic zone, which can be challenging due to the subtle imaging features. The aim of this project was to provide an in‐depth electro‐clinical characterization of MOGHE in patients with medically intractable epilepsy, and to assess the role of stereo‐electroencephalography (SEEG) in tailoring the resection and optimizing surgical outcome. Methods: This single‐center retrospective study analyzes a cohort of patients with medically intractable focal epilepsy who underwent surgery and had confirmed MOGHE on pathology evaluation. Clinical data, including demographics, electroclinical features (scalp EEG and invasive monitoring when available), surgical interventions, and postoperative outcomes were extracted from electronic medical records. Results: Of 23 patients identified, 10 (43%) underwent SEEG as part of their standard care. Seizure outcome data were available for 22 patients in this series. Median post‐operative follow‐up duration was 3.8 years. Fourteen patients (64%) were seizure‐free (Engel 1). Seizure freedom in the SEEG group was 80% ( n = 8/10), in comparison to the non‐SEEG group (50%, n = 6/12). Success rate was related to complete resection of the regions sampled by SEEG electrodes involved in ictal onset, and a more extensive resection of the lesion (or near total lobectomy). Significance: Our results underscore the pivotal role of SEEG in enhancing surgical outcomes in patients with drug‐resistant epilepsy due to MOGHE. SEEG proved particularly beneficial in defining resection margins, especially in cases where non‐invasive data were discordant, scalp EEG patterns were generalized or poorly localized, and imaging findings were nonspecific, diffuse, or normal, making lesion identification challenging.

Accurate localization of the theoretical epileptogenic zone in cingulate epilepsy is particularly challenging due to the region’s deep anatomical location and complex connectivity. While invasive stereoelectroencephalography (sEEG) methodology offers excellent spatiotemporal sampling of deep intracerebral structures, interpretation of these high-dimensional recordings remains largely qualitative and subject to interpretation by clinician experts. To address this limitation, we propose a quantitative, biomarker-based framework using phase–amplitude coupling (PAC) to investigate 25 seizures recorded from four patients with complex cingulate epilepsy who underwent sEEG followed by surgical treatment (either laser ablation or open resection), achieving ≥ 1 year of sustained seizure freedom. PAC values were computed from sEEG electrode contacts across multiple seizures during pre-ictal and ictal phases, employing wide-frequency and band-specific frequency coupling approaches. Among frequency pairs, theta–beta ([ ]–[ ]) coupling consistently demonstrated the most robust differentiation between surgically-treated and untreated contact sites. Our findings highlight frequency-specific PAC-based metrics as a potential tool for mapping dynamic epileptiform activity in brain networks, offering quantitative insight that may refine surgical planning and decision-making in challenging cases of cingulate epilepsy.

Objective. Multifractal formalism introduces an invaluable framework for the investigation of nonlinear, scale-invariant features across multiple time scales in non-stationary time series data. Approach. In this context, we sought to explore multifractal features defining spatiotemporal correlations in seizure activity, by applying multifractal detrended fluctuation analysis (MFDFA) to stereoelectroencephalography (sEEG) recordings from five patients with refractory, focal temporal epilepsy, who underwent subsequent surgical removal of the temporal lobe and achieved seizure freedom. Main results. To the best of our knowledge, we are the first to report evidence for a multifractal architecture underscoring sEEG-recorded epileptiform signals in vivo, suggesting a fundamental propensity for scale-invariance in electrophysiological human brain recordings. Importantly, dynamical MFDFA-derived features captured altered spatiotemporal trends through the pre-ictal, ictal and post-ictal states, and also across anatomical brain regions. Larger fluctuations (deviations) in these metrics were observed to varying extents across resected temporal lobe structures, as compared to more constrained dynamics in non-resected networks. Significance. MFDFA-derived metrics were statistically analyzed and found to capture unique features from the sEEG data, with temporal variations across anatomical brain networks offering a potentially useful tool for the visualization, quantification and interpretation of network involvement in the onset and evolution of seizure activity. These results underscore the importance of investigating high-complexity dynamics in intracranial sEEG recordings and their potential utility towards surgical decision-making in patients with medically intractable epilepsy.

Objective: To investigate whether local lesions created by stereo‐electroencephalography (SEEG)–guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug‐resistant epilepsy (DRE).Methods: Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico‐cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post‐stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non‐coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration.Results: RFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non‐coagulated contacts distant from coagulation site (range: 1.09–85 mm, median = 17.7 mm, interquartile range [IQR] 10.1–32.3). Contact pairs involved in significantly altered non‐coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC.Significance: This study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.