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.

项目概要/摘要 局灶性癫痫是一种网络疾病，其特征是局灶性皮质过度兴奋和大脑相互连接 影响兴奋性的区域。对于许多患者来说，准确定位所涉及的大脑区域具有挑战性 癫痫发作起始并确定影响个体兴奋性的癫痫网络节点。 我们假设与癫痫发作相关的脑组织长期受损并表现出异常、发作间期、 可以通过刺激动态地询问过度兴奋性。我们建议使用新颖的刺激—— 基于生物标志物来开发可靠且精确的癫痫发作位置和相关网络估计 节点。而基于刺激的生物标记物通常利用单脉冲电刺激来 地图连接性，我们提出了两种利用多个刺激脉冲的诊断刺激生物标志物， 新颖的波形和时变幅度包络来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 可以作为植入设备目标的连接。我们利用同步单机录音来 支持我们提出的过度兴奋的侵入性脑电图生物标志物。 我们的目标是：1) 开发基于刺激的癫痫发作区生物标志物，2) 识别患者- 特定的、调节性的网络连接，以及 3) 确定是否存在发作间期的单个神经元 过度兴奋的特征。为此，我们将使用新开发的外部刺激器 对植入临时侵入性设备的癫痫患者的 128-256 个通道进行自动、有效的刺激 电极。微电极的同步记录将使我们能够关联单个和多个单元的活动 从大电极记录脑电图活动。我们将在新颖的数学模型中检查这些结果 分数动力学框架，可以将反应的时间尺度与兴奋性联系起来。 资助成果将包括使用基于刺激的发作间期生物标志物来定位的快速方案 癫痫发作区域并识别相关网络节点。微电极记录将提供 对脑电图兴奋性动力学的单/多单元尺度理解。该提案探索了很大程度上未知的领域 基于刺激的生物标志物领域超越单脉冲电刺激，以改善治疗 耐药性癫痫。