Successful outcomes in epilepsy surgery rely on the accurate localization of the seizure onset zone (SOZ). Localizing the SOZ is often a costly and time-consuming process wherein a patient undergoes intracranial EEG (iEEG) monitoring, and a team of clinicians wait for seizures to occur. Clinicians then analyze the iEEG before each seizure onset to identify the SOZ, and localization accuracy increases when more seizures are captured. In this study, we develop a new approach to guide clinicians to actively elicit seizures with electrical stimulation. We hypothesize that a brain region belongs to the SOZ if a periodic stimulation at a particular frequency produces large amplitude oscillations in the iEEG network that propagate seizure activity. Such responses occur when there is “resonance” in the iEEG network, and the resonant frequency can be detected by observing a sharp peak in the magnitude versus frequency response curve, called a bode plot. To test our hypothesis, we analyzed single-pulse electrical stimulation (SPES) response data in 32 epilepsy patients undergoing iEEG monitoring. For each patient and each stimulated brain region, we constructed a bode plot by estimating a transfer function model (TFM) from the iEEG “impulse” or SPES response. The bode plots were then analyzed for evidence of resonance. First, we showed that when bode plot features were used as a marker of the SOZ, it distinguished successful from failed surgical outcomes with an AUC of 0.83, an accuracy that surpassed current methods of analysis with cortico-cortical evoked potential amplitude (CCEPs) and cortico-cortical spectral responses (CCSRs). Then, we retrospectively showed that three out of five native seizures accidentally triggered in four patients during routine periodic stimulation at a given frequency corresponded to a resonant peak in the bode plot. Lastly, we prospectively stimulated peak resonant frequencies gleaned from the bode plots to elicit seizures in six patients, and this resulted in an induction of three seizures and three auras in these patients. These findings suggest neural resonance as a new biomarker of the SOZ that can guide clinicians in eliciting native seizures to more quickly and accurately localize the SOZ.

中文翻译：

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用神经共振刺激自然癫痫发作：一种定位癫痫发作区的新方法

癫痫手术的成功结果取决于癫痫发作区 (SOZ) 的准确定位。定位 SOZ 通常是一个昂贵且耗时的过程，其中患者接受颅内脑电图 (iEEG) 监测，临床医生团队等待癫痫发作。然后，临床医生在每次癫痫发作前分析 iEEG 以确定 SOZ，并且当捕获到更多癫痫发作时定位精度会提高。在这项研究中，我们开发了一种新方法来指导临床医生通过电刺激主动引发癫痫发作。我们假设如果特定频率的周期性刺激在传播癫痫发作活动的 iEEG 网络中产生大幅度振荡，则大脑区域属于 SOZ。当 iEEG 网络中存在“共振”时，就会出现这种反应，并且可以通过观察幅度与频率响应曲线（称为波德图）中的尖峰来检测共振频率。为了验证我们的假设，我们分析了 32 名接受 iEEG 监测的癫痫患者的单脉冲电刺激 (SPES) 反应数据。对于每个患者和每个受刺激的大脑区域，我们通过从 iEEG“脉冲”或 SPES 响应估计传递函数模型 (TFM) 来构建波德图。然后分析波特图以获得共振的证据。首先，我们展示了当波德图特征被用作 SOZ 的标记时，它以 AUC 为 0.83 区分成功与失败的手术结果，其准确性超过了当前的皮质-皮质诱发电位振幅 (CCEP) 分析方法，并且皮质-皮质光谱反应 (CCSR)。然后，我们回顾性地表明，在给定频率的常规周期性刺激期间，四名患者意外触发的五分之三的自然癫痫发作对应于波德图中的共振峰。最后，我们前瞻性地刺激了从波德图收集到的峰值共振频率，以引发 6 名患者的癫痫发作，这导致这些患者诱发了 3 次癫痫发作和 3 种先兆。这些发现表明，神经共振作为 SOZ 的一种新生物标志物，可以指导临床医生诱发自然发作，从而更快、更准确地定位 SOZ。我们前瞻性地刺激了从波德图收集到的共振峰值频率，以引发 6 名患者的癫痫发作，这导致这些患者诱发了 3 次癫痫发作和 3 种先兆。这些发现表明，神经共振作为 SOZ 的一种新生物标志物，可以指导临床医生诱发自然发作，从而更快、更准确地定位 SOZ。我们前瞻性地刺激了从波德图收集到的共振峰值频率，以引发 6 名患者的癫痫发作，这导致这些患者诱发了 3 次癫痫发作和 3 种先兆。这些发现表明，神经共振作为 SOZ 的一种新生物标志物，可以指导临床医生诱发自然发作，从而更快、更准确地定位 SOZ。