Graph-Based Approaches to Learning Epileptogenic Zone Localization Using Stereo-EEG Recordings

The epileptogenic zone (EZ) is the brain region that generates seizures in an individual, and is the target of epilepsy surgery. Localizing the EZ from stereo-EEG (sEEG) recordings supports surgical planning, but manual interpretation is time-consuming and focuses on seizure recordings. Graphical learning models of resting-state functional connectivity among the recorded brain regions are an attractive alternative, but depend crucially on the network topology chosen for the model. We present a controlled study of graph-based models to explore how graph topology affects EZ localization from resting-state sEEG in 40 patients. Using the same simple learnable model and leave-one-patient-out evaluation, we compare dense graphs, anatomy- and geometry-informed priors, budgeted sparsification methods, and learned sparsification, including the proposed Region-Bridge-$c$ topology. To compare graph constructions fairly, we control the number of incoming edges per node and vary graph sparsity. At $\approx 30\%$ edge retention, Region-Bridge-$c$ achieves the highest observed mean PR-AUC ($0.371\pm0.015$; ROC-AUC $0.743\pm0.010$) while using $\approx 69\%$ fewer edges than Dense (PR-AUC $0.349\pm0.014$). Spatial-$k$ is competitive, whereas random pruning requires near-dense retention. Learned sparsification benefits from anatomical node metadata but, on average, does not surpass the best fixed prior. Across all topologies, the best choice varies by patient. These results suggest that graph construction should be evaluated explicitly rather than treated as fixed preprocessing.

Teaching LLMs to Recommend and Defer in Underrepresented Epilepsy Care

Specialist epilepsy expertise is scarce in resource-constrained settings, making LLM-based decision support attractive for frontline clinicians managing longitudinal treatment. Such systems must adapt to local prescribing practice and know when to defer. We study this problem in Ugandan pediatric epilepsy care, predicting anti-seizure medication regimens from longitudinal unstructured clinic notes. Standard prompting achieves non-trivial agreement with physician prescriptions, but neurologist review shows that many errors reflect distribution-miscalibrated prescribing defaults rather than failures to parse the local record. We introduce MANANA, a non-parametric prompt-learning framework that learns local prescribing guidance from a small patient-level training set. MANANA converts observed prescription errors into auditable prompt memories, instantiated in single-agent and multi-agent variants, and improves over classical ML models, direct LLM prompting, and prompt-optimization baselines across two independently collected Ugandan cohorts. We further propose Bayesian prompt averaging, which converts the learned prompt trajectory into prescription likelihoods and an uncertainty-based deferral signal. On the independently collected held-out cohort, this improves visit-level top-3 prescription accuracy by 4-8 percentage points over prompt-optimization baselines and enables selective prediction: the system can auto-handle the most confident half of cases at 95% precision, or the most confident quarter at 99% precision, while deferring lower-confidence cases for specialist review.

Foundation Models for Epileptogenic Zone Identification in Drug-Resistant Epilepsy

Accurate identification of the epileptogenic zone (EZ) is essential for seizure freedom after resective surgery in drug-resistant epilepsy, yet seizure freedom rates remain below 50%. We developed EpiiSLM, a dual foundation model system for EZ identification with stereo-electroencephalography (sEEG), by training a signal foundation model on 104,990 minutes of sEEG recordings from the Montreal Neurological Institute & Hospital, while leveraging all recordings regardless of surgical outcome and anchoring EZ biomarker extraction on non-epileptic signals. A language foundation model then integrates sEEG-derived outputs with multimodal clinical information to produce interpretable predictions. Under leave-one-patient-out evaluation, EpiiSLM achieved 0.978 contact-level positive predictive value (PPV), outperforming the seizure onset zone(SOZ)-as-EZ baseline by 15.1% (p < 0.05), and 100% region-level accuracy; on an external dataset, EpiiSLM achieved 0.857 contact-level PPV. EpiiSLM requires only one night of interictal sleep data, suggesting potential to reduce invasive sEEG monitoring duration and improve surgical outcomes.

Poisson Flow of Cortical Folding in Juvenile Myoclonic Epilepsy

Cortical folding reflects coordinated neurodevelopmental processes and is increasingly recognized as a sensitive marker of neurological disease. However, most existing analyses rely on indirect scalar summaries that do not explicitly model folding geometry itself. In juvenile myoclonic epilepsy (JME), a common genetic epilepsy, cortical abnormalities are often subtle, spatially distributed, and difficult to detect using conventional morphometric measures. We introduce a Poisson-equation--based framework that models cortical folding as a geometry-driven flow derived from mean curvature on the cortical manifold. By treating folding patterns as a stationary source--sink structure, the proposed approach yields a smooth, globally balanced potential field whose surface gradient defines a physically interpretable flux. This framework enables spatially coherent analysis of sulcal--gyral folding organization and provides a principled representation of geometry-driven cortical structure in JME.

Literature-Guided Minimax Optimization of Virtual Epilepsy Neurostimulation

Computational models of epilepsy promise patient-specific treatment design, but most optimization workflows still search for parameters that perform well on average. In neuromodulation, this is a weak target: a protocol that improves the mean response can still fail in the patient whose network is least tolerant to stimulation. We present a literature-guided minimax pipeline that couples PubMed-scale hypothesis extraction, The Virtual Brain (TVB) Epileptor simulations, and large-language-model-guided black-box optimization. The optimizer proposes either intrinsic model-control parameters or clinically interpretable external-stimulation protocols; TVB evaluates each proposal across sampled virtual patients; and the objective maximizes worst-case reward, defined as the negative variance of simulated seizure activity. In the intrinsic model-control experiment, the best archived parameter set improved worst-case reward from -0.5285 to -0.3182, a 39.8% gain over baseline. The clinical-style external-stimulation search produced a much smaller worst-case improvement (1.7%), and a 20-patient virtual cohort showed no aggregate benefit (p=0.9019), despite a 55% responder rate and a positive temporal-lobe subgroup signal. The study should be read as an in silico proof of concept for robust, literature-aware neurostimulation design, not as clinical evidence.