Intraoperative Localization of Epileptic Brain Regions Under Sevoflurane Anesthesia.

耐药的局灶性癫痫影响数以百万计的儿童，治疗往往需要侵入性评估。这 过程需要识别颅内脑电(IEEG)生物标志物，例如棘波和波 放电(SWD)，以指导外科手术切除推测的致痫区域负责产生 习惯性癫痫发作。在儿科患者中，术外iEEG证据表明，SWD替代测量 增量波相位和高频振荡(HFO)调幅指数(MI)之间的耦合- 准确跟踪癫痫的致病作用。由于MI没有详细说明神经传播的因果关系，它的强大之处在于 还可以考虑iEEG传递熵(TE)，它测量有效的连通性，以及动态示踪 提供合理的传播途径。当然，捕捉到足够的发作间歇期和发作期癫痫事件通常 需要数天的非手术iEEG记录，这一过程令人精疲力竭，费用高昂，而且充满了 重大风险因素。因此，术中诱导和可靠测量的技术的发展 癫痫iEEG生物标志物势在必行，以避免上述陷阱，并有助于扩大一期应用 程序。与之相关的是，七氟醚麻醉可逆地激活了棘波活动，但仍有很多争议 关于它的专一性。儿童iEEG的初步结果表明，七氟醚可在术中增强 MI和HFO在癫痫灶的有效连接(TE)。然而，需要大量的队列研究来验证 这一发现，因为尚不清楚七氟醚如何影响健康组和对照组术中MI和HFO-TE。 如果这些信号通过主要的脑白质束传播。因此，该计划的主要目标是 目前的建议是：1)建立术中MI和HFO-TE的标准化图谱， 七氟醚的浓度，以及2)确定七氟醚诱导的这些特征的调制是否可以 定位癫痫发作灶并预测癫痫发作结果。为了实现这些目标，实习生将绘制患者地图 电极到三维磁共振脑图像，量化术中iEEG指标 逐步增加七氟醚的用量，并结合iEEG有效连接性和脑白质描记(即 动态跟踪成像)。表征MI和HFO有效连通性的内生分布， 如果没有七氟醚，将为iEEG解释提供关键的基线参考。此外，理解 七氟醚如何影响癫痫网络中的这些指标有望改善发作间期定位工作 在手术期间，通过减少对手术外记录的需求来减少侵入性诊断负担，优化 治疗成本效益，并最终改善癫痫发作结果。通过这个项目，学员将：(1) 洞察并帮助改进癫痫的临床治疗，(2)加强对神经如何 七氟醚下的振荡耦合和有效连通反应，以及(3)将接受训练方案 促进批判性思维和假设驱动、伦理研究设计的发展。累积效应 这项研究和教学将为学员作为内科科学家的职业生涯提供一个重要的基础。

Drug-resistant, focal epilepsy impacts millions of children, and treatment often requires invasive evaluation. This process entails identification of intracranial electroencephalography (iEEG) biomarkers such as spike-and-wave discharges (SWDs), to guide surgical removal of the presumed epileptogenic zone responsible for generating habitual seizures. In pediatric patients, extra-operative iEEG evidence indicated that a SWD proxy measuring coupling between delta wave phase and high-frequency oscillation (HFO) amplitude – Modulation Index (MI) – accurately tracks epileptogenicity. Since MI does not detail the causality of neural propagations, it’s powerful to also consider iEEG Transfer Entropy (TE), which measures effective connectivity, and dynamic tractography to provide plausible propagation pathways. Granted, capturing adequate interictal and ictal epileptic events often requires days of extra-operative iEEG recording, and this procedure is grueling, expensive, and replete with major risk factors. Thus, development of intra-operative techniques for induction and reliable measurement of epileptic iEEG biomarkers is imperative to avoid the above pitfalls and help expand utility of one-stage procedures. Pertinently, sevoflurane anesthesia reversibly activates spike activity, but there is much debate over its specificity. Preliminary iEEG results in children suggest that sevoflurane may intra-operatively augment both MI and HFO effective connectivity (TE) in seizure foci. However, large cohort studies are needed to validate this finding, as it is unknown how sevoflurane impacts intra-operative MI and HFO-TE in healthy versus epileptogenic brain areas and if these signals spread via major white matter tracts. Thus, the main aims of the current proposal are to: 1) build normative atlases of intra-operative MI and HFO-TE, at varying concentrations of sevoflurane, and 2) determine if sevoflurane-induced modulation of these features can localize seizure foci and predict seizure outcomes. To accomplish these aims, the trainee will map patient electrodes to 3-dimensional magnetic resonance brain images, quantify the intra-operative iEEG metrics at stepwise increases of sevoflurane, and combine iEEG effective connectivity with white matter tractography (i.e. dynamic tractography). Characterizing the endogenous distribution of MI and HFO effective connectivity, with and without sevoflurane, will provide critical baseline reference for iEEG interpretation. In addition, understanding how sevoflurane impacts these metrics in epileptic networks is expected to improve interictal localization efforts during surgery, reduce invasive diagnostic burden by mitigating the need for extra-operative recording, optimize treatment cost effectiveness, and ultimately improve seizure outcomes. Through this project, the trainee will: (1) gain insight into and help refine clinical epilepsy treatment, (2) enhance scientific understanding of how neural oscillatory coupling and effective connectivity respond under sevoflurane, and (3) will undergo a training regimen to foster development of critical thinking and hypothesis-driven, ethical research design. The cumulative effect of the research and didactics will provide a critical foundation for the trainee’s career as a physician-scientist.