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: 10290984
• 负责人: Nuri Firat Ince
• 金额: $ 98.02万
• 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/10290984
• 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; 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; base; clinical practice; implantable device; improved; machine learning algorithm; neural implant; neurotechnology; neurotransmission; open source; prevent; relating to nervous system; 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

项目概要： 颅内脑电图 (iEEG) 的高频振荡 (HFO) 有可能识别手术切除 耐药性癫痫患者的癫痫发作区/癫痫发作区（SOZ）。然而，多份报告表明 HFO 不仅可以由癫痫性脑组织产生，还可以由非癫痫部位产生，通常包括 口才区域，如运动皮质、视觉皮质和语言皮质。在这个项目中，我们提出了初步证据 反复出现的波形模式可能足以区分病理性 HFO 和生理性 HFO。 具体来说，我们表明 SOZ 反复生成具有相似特征的典型 HFO 集。 波形形态，而从 SOZ 之外记录的事件是不规则的。这种形态学 模式作为一种强大的神经生物标志物，将 SOZ 与多个患者的其他大脑区域隔离 始终如一。虽然这些有希望的初步结果已经到位，但刻板印象的功能效用 闭环癫痫控制系统中的 HFO 仍然未知。 截至目前，尚不清楚 SOZ 产生的定型 HFO 是否可以用 植入式系统。如果这一点能够实现，那么 HFO 就可以作为神经生物标记物战略性地转化为 闭环癫痫控制应用。我们假设病理定型 HFO 可以被捕获 通过 CorTec 的植入式大脑交换 (BIC) 系统和这些事件的空间拓扑可以 植入系统利用它来提供有针对性的电刺激以实现癫痫控制。使用 癫痫监测单元（EMU）内的急性设置，该项目将研究捕获的可行性 使用新的 BIC 系统对 HFO 事件进行定型，并将检测结果与使用 市售放大器。如果我们研究的第一阶段（Aim-1）取得成功，那么在稍后的阶段 第二阶段（Aim-2），再次在动车组中，我们将向这些大脑部位提供有针对性的电刺激 使用 BIC 与定型 HFO 关联。我们将研究这个闭环的调节作用 通过监测尖峰、癫痫放电、波纹等特征事件的变化来制定刺激策略 和快速的涟漪。 如果成功，这个闭环系统不必等待癫痫发作开始才能传递刺激 在它开始时，由 Neuropace 的 RNS 系统完成。相比之下，系统将监测空间地形 和定型 HFO 的比率，并向这些区域提供有针对性的刺激，以防止癫痫发作。 如果我们在急性环境下的研究取得成功，我们将进行临床试验并运行我们的 在慢性非卧床环境中使用植入的 BIC 系统的方法。 1