arXiv:2606.04339cs.LG2026-06

针对癫痫神经刺激的个性化治疗,提出基于文献的鲁棒优化方法。

Literature-Guided Minimax Optimization of Virtual Epilepsy Neurostimulation

论文配图:Literature-Guided Minimax Optimization of Virtual Epilepsy Neurostimulation
图 1 · 摘自论文原文
  • 结合文献提取与脑模拟,以最差情况表现为目标进行参数优化
  • 内在参数优化使最差情况性能提升39.8%,外在刺激优化仅提升1.7%
  • 适合追求治疗鲁棒性的神经调控研究者,非临床证据

计算模型有望实现癫痫患者的个性化治疗设计,但现有优化流程多关注平均性能。在神经调控中,平均表现优异的方案仍可能对网络耐受性最差的患者失效。本文提出一种文献引导的极小极大优化流程,整合PubMed级假设提取、虚拟大脑(TVB)Epileptor仿真及大语言模型驱动的黑箱优化。优化器可生成内在模型参数或临床可解释的外部刺激方案;TVB在采样的虚拟患者群体中评估每项提议;目标函数最大化最差情况奖励,即模拟发作活动方差的负值。在内在参数实验中,最优参数集将最差情况奖励从-0.5285提升至-0.3182,较基线提升39.8%。临床风格的外部刺激搜索仅带来1.7%的最差情况改进,20名虚拟患者队列未见整体改善(p=0.9019),尽管应答率达55%,颞叶亚组显示阳性信号。该研究为鲁棒、文献驱动的神经刺激设计提供了一个体内概念验证,而非临床证据。

原文摘要 · Abstract (English)

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.

癫痫治疗神经刺激优化算法虚拟脑

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