Acute Modulation of Stereotyped High Frequency Oscillations with a Closed-Loop Brain Interchange System in Drug Resistant Epilepsy

耐药性癫痫中闭环脑交换系统对刻板高频振荡的急性调节

• 批准号: 10478109
• 负责人: Nuri Firat Ince
• 金额: $ 70.13万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10478109
• 关键词: Acute; Amplifiers; Area; Austria; Brain; Brain region; Cerebrum; Characteristics; Chronic; Clinical; Clinical Trials; Computer software; Data; Detection; Electric Stimulation; Electroencephalography; Epilepsy; Event; Excision; Frequencies; High Frequency Oscillation; Implant; Intractable Epilepsy; Laboratories; Language; Location; Methods; Monitor; Morphology; Motivation; Motor; Neurologic Deficit; Operative Surgical Procedures; Outcome; Pathologic; Patients; Pattern; Phase; Physicians; Physiological; Recurrence; Reporting; Research; Resolution; Resources; Risk; Role; Running; Sampling; Scheme; Seizures; Site; Stereotyping; Structure; System; Testing; Time; Tissues; Translating; Visual; clinical practice; implantable device; improved; machine learning algorithm; neural; neural implant; neurosurgery; neurotechnology; neurotransmission; open source; prevent; response; success; time use; tool

Project Summary: High frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual and language cortices. In this project, we present the initial evidence of a recurrent waveform pattern that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, we show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. We hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier. If the first phase (Aim-1) of our study becomes successful, later in the second phase (Aim-2), once again in the EMU, we will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC. We will investigate the modulatory effects of this closed-loop stimulation strategy by monitoring the changes in signature events such as spikes, epileptic discharges, ripples and fast ripples. If successful, this closed-loop system does not have to wait for a seizure to start in order to deliver the stimulation at its onset as done by the RNS system of Neuropace. In contrast, the system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these areas to prevent seizures from occurring. If the outcomes of our research in acute setting become successful, we will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting. 1

项目摘要： 颅内脑电图（IEEG）的高频振荡（HFO）具有识别手术切除的潜力 耐药性癫痫患者的面积/癫痫发作区（SOZ）。但是，多个报告表明 HFO不仅可以通过癫痫脑组织产生 雄辩的区域，例如运动，视觉和语言皮层。在这个项目中，我们提供了 复发性波形模式，可能足以区分病理HFO和生理HFO。 具体而言，我们表明SOZ反复生成了具有相似的刻板印象HFO 波形形态，而从SOZ中记录的事件是不规则的。这种形态学 模式是一种可靠的神经虫标志物，可将SOZ与多个患者的其他大脑区域分离出来 一贯。尽管这些有希望的初步结果已经到位，但刻板印象的功能实用性 闭环癫痫控制系统中的HFO仍然未知。 截至今天，尚不清楚SOZ产生的刻板印象是否可以用 植入系统。如果可以实现这一目标，则可以将HFO策略性地翻译成神经虫标志物 闭环癫痫发作控制应用。我们假设可以捕获病理刻板印象的HFO 使用Cortec的可植入大脑互换（BIC）系统和这些事件的空间形态可以是 可植入系统利用可提供靶向电刺激以实现癫痫发作。使用一个 癫痫监测单元（EMU）中的急性设置，该项目将调查捕获的可行性 使用新的BIC系统进行定型的HFO事件，并将检测结果与获得的检测结果进行比较 市售的放大器。如果我们的研究的第一阶段（AIM-1）成功了，那么 第二阶段（AIM-2），再次在EMU中，我们将向这些大脑部位传递目标电刺激 使用BIC与刻板印象的HFO相关。我们将研究此闭环的调节作用 通过监视签名事件的变化，例如尖峰，癫痫放电，涟漪，刺激策略 和快速的涟漪。 如果成功的话，这种闭环系统不必等待癫痫发作才能开始刺激 在INS Neuropace系统完成的一开始。相比之下，系统将监视空间地形 刻板印象的HFO并将有针对性的刺激传递到这些区域，以防止癫痫发作发生。 如果我们在急性环境中的研究结果成功，我们将执行临床试验并进行我们的运行 在慢性卧床环境中使用植入BIC系统的方法。 1

项目成果

A sparse representation strategy to eliminate pseudo-HFO events from intracranial EEG for seizure onset zone localization.

• DOI: 10.1088/1741-2552/ac8766
• 发表时间: 2022-08-24
• 期刊: JOURNAL OF NEURAL ENGINEERING
• 影响因子: 4
• 作者: Besheli, Behrang Fazli;Sha, Zhiyi;Gavvala, Jay R.;Gurses, Candan;Karamursel, Sacit;Quach, Michael M.;Curry, Daniel J.;Sheth, Sameer A.;Francis, David J.;Henry, Thomas R.;Ince, Nuri F.
• 通讯作者: Ince, Nuri F.

Long-latency gamma modulation after median nerve stimulation delineates the central sulcus and contrasts the states of consciousness

• DOI: 10.1016/j.clinph.2022.10.008
• 发表时间: 2022-11-10
• 期刊: CLINICAL NEUROPHYSIOLOGY
• 影响因子: 4.7
• 作者: Asman，Priscella;Pellizzer，Giuseppe;Ince，Nuri F.
• 通讯作者: Ince，Nuri F.

Elimination of pseudo-HFOs in iEEG using sparse representation and Random Forest classifier.

• DOI: 10.1109/embc48229.2022.9871447
• 发表时间: 2022-07
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference