Magnetoencephalographic detection of high-frequency activity in epilepsy patients

描述（由申请人提供）：我们建议识别人类大脑中导致癫痫发作的不寻常类型的电活动。癫痫是一种反复发作的倾向，影响了0.5%的人口。虽然许多癫痫患者对药物有反应，但有10%在医学上是难治性的。如果癫痫发作的来源可以定位在大脑（癫痫发生区，EZ），手术切除该组织是可能的。在简单的病例中，80%的患者在手术后不再癫痫发作，从而显著改善了生活质量。然而，本地化EZ是一个挑战。当传统技术失败时，可以通过手术植入硬膜下电极来发现癫痫发作或间歇尖峰。在这些病例中，只有50%接受后续手术的患者不再癫痫发作。为了改善这些患者的EZ定位和手术效果，我们建议研究高频低压活动（HFLV），而不是目前定位间隙尖峰的做法。HFLV是一种最近与EZ相关的脑皮层电活动，包括发作间期和发作时。虽然其他人已经通过手术植入硬膜下电极（皮质电成像，ECoG）检测HFLV，但我们将尝试使用无创方法识别HFLV。具体来说，我们将使用脑磁图（MEG），它检测由神经元电流产生的颅外磁场。在我们研究的回顾性阶段，我们将在存档的脑电图和脑磁图记录中识别HFLV，并确定这些方法之间的空间一致性。然后，我们将确定在随后的手术中去除HFLV相关组织是否与癫痫发作自由相关。因此，我们将确定MEG是否是一种足以替代ECoG的无创HFLV鉴定方法，并验证HFLV的临床重要性。在前瞻性阶段，我们将对符合癫痫手术条件的患者系统地使用MEG和ECoG，并确定哪些HFLV频带（亚型）与癫痫发生区最相关。我们还将在这一前瞻性阶段研究手术结果和切除组织的病理，以更好地了解HFLV的重要性。我们相信本项目的完成将促进对癫痫发生的科学认识，更重要的是提高癫痫患者手术治疗的疗效。

DESCRIPTION (provided by applicant): We propose to identify unusual types of electrical activity in the human brain that lead to seizures. Epilepsy, a tendency toward recurrent seizures, affects 0.5% of the population. While many patients with epilepsy respond to medication, 10% are medically refractory. If the source of seizures can be localized in the brain (the epileptogenic zone, EZ), surgical removal of that tissue may be possible. In straightforward cases, 80% of patients become seizure-free after such surgery, leading to significant improvements in quality-of-life. However, localizing the EZ is challenging. When traditional techniques fail, subdural electrodes may be surgically implanted to find the seizure onset or interictal spikes. In these cases, only 50% of patients receiving subsequent surgery become seizure-free. To improve EZ localization and surgical outcomes for these patients, we propose studying high-frequency low-voltage activity (HFLV), instead of the current practice of localizing interictal spikes. HFLV is a type of electrical cortical activity that has recently been associated with the EZ, both interictally and at seizure onset. While others have detected HFLV using surgically implanted subdural electrodes (electrocorticography, ECoG), we will attempt to identify HFLV using noninvasive methods. Specifically, we will use the magnetoencephalogram (MEG), which detects extracranial magnetic fields produced by neuronal current flow. In the retrospective phase of our study, we will identify HFLV in archived ECoG and MEG recordings, and determine the spatial concordance between these methods. We will then determine if removal of HFLV- associated tissue in subsequent surgery correlated with seizure freedom. We will thereby determine whether MEG is an adequate noninvasive alternative to ECoG for HFLV identification, and also validate HFLV's clinical importance. In the prospective phase, we will use MEG and ECoG systematically in patients eligible for epilepsy surgery, and determine which HFLV frequency bands (subtypes) best correlate with the epileptogenic zone. We will also study surgical outcomes and pathology of resected tissue in this prospective phase, to better understand the importance of HFLV. We believe completion of this project will advance the scientific understanding of epileptogenesis, and more importantly, improve the efficacy of epilepsy surgery for patients with this disease. PUBLIC HEALTH RELEVANCE: Localizing brain tissue responsible for seizures is challenging, but can lead to surgery that may reduce - or even eliminate - seizures for patients with epilepsy. To help identify this tissue, we will study high- frequency low-voltage electrical activity in the brain, whose importance in generating seizures was only recently recognized. We will use invasive (electrocorticography) and noninvasive (magnetoencephalography) techniques to identify this activity, and determine if its presence and location impacts the success of epilepsy surgeries.