Literature-Guided Minimax Optimization of Virtual Epilepsy Neurostimulation
This work provides an in silico proof of concept for robust, literature-aware neurostimulation design, but the results are preliminary and not clinically validated.
The authors present a literature-guided minimax optimization pipeline for epilepsy neurostimulation that uses PubMed-scale hypothesis extraction, The Virtual Brain simulations, and LLM-guided black-box optimization to maximize worst-case reward. In intrinsic model-control experiments, the method improved worst-case reward by 39.8% over baseline, but clinical-style external-stimulation search showed minimal improvement (1.7%) and no aggregate benefit in a 20-patient virtual cohort.
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.