Novel diagnostic stimulation to quantify cortical excitability and guide epilepsy therapy

量化皮质兴奋性并指导癫痫治疗的新型诊断刺激

• 批准号: 10559958
• 负责人: Brian Nils Lundstrom
• 金额: $ 40.35万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10559958
• 关键词: Admission activity; Affect; Anticonvulsants; Area; Awareness; Biological Markers; Brain; Brain region; Chronic; Clinical; Devices; Diagnosis; Diagnostic; Disease; Electric Stimulation; Electrodes; Electroencephalography; Epilepsy; Evoked Potentials; Exhibits; Feedback; Goals; Grant; High Frequency Oscillation; Implant; Individual; Inpatients; Intractable Epilepsy; Link; Location; Maps; Mathematics; Methods; Microelectrodes; Monitor; Morbidity - disease rate; Neurons; Outcome; Partial Epilepsies; Patients; Periodicals; Physiologic pulse; Protocols documentation; Refractory; Research; Sampling; Seizures; Source; Technology; Therapeutic; Time; brain tissue; epileptiform; experience; implantable device; improved; insight; neural implant; neurosurgery; novel; novel diagnostics; response; success

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.

项目摘要/摘要 局灶性癫痫是一种网络疾病，以皮质过度兴奋性和互连大脑的焦点区域为标志 影响兴奋性的区域。对于许多患者，准确定位涉及的大脑区域是一项挑战 在癫痫发作中，并确定癫痫发作网络的节点，这些癫痫发作网络会影响单独的兴奋性。 我们假设与癫痫发作相关的脑组织长期损害，并且表现出异常，间歇性， 可以使用刺激动态询问的过度兴奋性。我们建议使用新型刺激 基于生物标志物来开发可靠和精确的癫痫发作位置和相关网络的估计值 节点。而基于刺激的生物标志物通常利用了电刺激的单个脉冲到 MAP连接性，我们提出了两个使用多种刺激脉冲的诊断刺激生物标志物， 新颖的波形和随时间变化的振幅信封，以询问适应和抑制反馈。 利用高通道计数刺激，我们建议一种快速映射调节网络的方法 可以用作植入设备目标的连接。我们将同时单位记录同时使用 基础我们提出的过度兴奋性侵入性EEG生物标志物。 我们的目的是：1）开发基于刺激的癫痫发作区的生物标志物，2）确定患者 - 特定的调节网络连接，以及3）确定是否存在发作单神经元 过度兴奋的签名。为此，我们将使用新开发的外部刺激器将允许 自动化，有效刺激128-256个通道，癫痫患者植入了临时侵入性的患者 电极。来自微电极的同时记录将使我们能够关联单个和多单位活动 从大椭圆形记录的脑电图活性。我们将在新颖的数学中检查这些结果 可以将响应的时间标准与兴奋性联系起来的分数动态框架。 授予结果将包括使用基于刺激的间隔生物标志物的快速方案来定位 癫痫发作区并确定相关的网络节点。微电极记录将提供 对脑电图兴奋性动力学的单个/多单元尺度理解。该提案探讨了在很大程度上未知的 基于刺激的生物标志物领域以外的单脉冲电刺激，以改善治疗 耐药性癫痫。