Novel diagnostic stimulation to quantify cortical excitability and guide epilepsy therapy

项目总结/摘要 局灶性癫痫是一种网络性疾病，其特征是局灶性皮质过度兴奋区和相互连接的大脑 影响兴奋性的区域。对于许多患者来说，准确定位涉及的大脑区域是具有挑战性的。 在癫痫发作开始和确定节点的癫痫发作网络，影响兴奋性的个人基础上。 我们假设癫痫相关的脑组织是长期受损的，表现出异常，发作间期， 可以使用刺激动态询问的过度兴奋。我们建议使用新的刺激- 基于生物标志物开发可靠和精确的癫痫发作位置和相关网络的估计 结而基于刺激的生物标志物通常利用电刺激的单脉冲来 地图连接，我们提出了两个诊断刺激生物标志物，利用多个刺激脉冲， 新颖的波形和随时间变化的幅度包络，以询问适应和抑制反馈。 利用高通道数刺激，我们提出了一种快速映射调制网络的方法， 可以作为植入器械目标的连接。我们利用同步的单个单元记录， 支持我们提出的侵入性脑电图生物标志物的过度兴奋。 我们的目标是：1）开发癫痫发作区的基于刺激的生物标志物，2）识别患者- 特异性、调节性网络连接，以及3）确定是否存在发作间期单个神经元 过度兴奋的特征为此，我们将使用一种新开发的外部刺激器， 在植入临时侵入性植入物的癫痫患者中自动有效刺激128-256个通道 个电极微电极的同步记录将使我们能够将单个和多个单位的活动联系起来 用大电极记录脑电图活动我们将在新的数学模型中检验这些结果。 分数动力学的框架，可以连接反应的时间尺度兴奋性。 资助结果将包括一个快速的协议，使用刺激为基础的发作间期生物标志物，以定位 癫痫发作区和识别相关网络节点。微电极记录将提供 EEG兴奋性动力学的单/多单位尺度理解。这项提议探索了在很大程度上未知的 单脉冲电刺激以外的基于刺激的生物标志物的领域，以改善 抗药性癫痫

PROJECT SUMMARY/ABSTRACT Focal epilepsy is a network disease marked by focal areas of cortical hyperexcitability and interconnected brain regions that affect excitability. For many patients, it is challenging to accurately localize brain regions involved in seizure initiation and to determine nodes of the seizure network that affect excitability on an individual basis. We hypothesize that seizure-related brain tissue is chronically compromised and exhibits aberrant, interictal, hyperexcitability that can be interrogated dynamically using stimulation. We propose using novel stimulation- based biomarkers to develop reliable and precise estimates of seizure onset locations and related network nodes. Whereas stimulation-based biomarkers have typically utilized single pulses of electrical stimulation to map connectivity, we propose two diagnostic stimulation biomarkers which utilize multiple stimulation pulses, novel waveforms and time-varying amplitude envelopes to interrogate adaptation and inhibitory feedback. Leveraging high-channel count stimulation, we suggest a method to rapidly map modulatory network connections which could serve as implanted device targets. We utilize simultaneous single unit recordings to underpin our proposed invasive EEG biomarkers of hyperexcitability. Our aims are to: 1) Develop stimulation-based biomarkers of the seizure onset zone, 2) Identify patient- specific, modulatory network connections, and 3) Determine whether there are interictal single neuron signatures of hyperexcitability. To do this, we will use a newly developed external stimulator will allow for automated, efficient stimulation of 128-256 channels in epilepsy patients implanted with temporary invasive electrodes. Simultaneous recordings from microelectrodes will allow us to correlate single and multiunit activity with EEG activity recorded from macroelectrodes. We will examine these results within the novel mathematical framework of fractional dynamics that can link the timescales of responses to excitability. Grant outcomes will include a rapid protocol using stimulation-based interictal biomarkers to localize the seizure onset zone and identify relevant network nodes. Microelectrode recordings will provide a single/multiunit scale understanding of EEG excitability dynamics. This proposal explores the largely uncharted territory of stimulation-based biomarkers beyond single pulse electrical stimulation to improve treatment for drug-resistant epilepsy.