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0.5%的人口。虽然许多癫痫患者对药物有反应，但10%的患者在药物上是难治性的。如果癫痫发作的来源可以定位在大脑(致痫区域，EZ)，那么手术切除该组织是可能的。在简单的情况下，80%的患者在这样的手术后癫痫发作消失，导致生活质量的显著改善。然而，将EZ本地化是具有挑战性的。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发作间期棘波。在这些病例中，接受后续手术的患者中只有50%的患者癫痫发作消失。为了改善EZ的定位和手术结果，我们建议研究高频低电压活动(HFLV)，而不是目前定位发作间期棘波的做法。HFLV是一种最近被认为与癫痫发作间期和癫痫发作时的EZ有关的皮层电活动。虽然其他人已经使用手术植入的硬膜下电极(皮质脑电图术，ECoG)检测到HFLV，但我们将尝试使用非侵入性方法来识别HFLV。具体地说，我们将使用脑磁图(MEG)，它检测神经元电流产生的颅外磁场。在我们研究的回顾阶段，我们将确定存档的ECoG和MEG记录中的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切除HFLV相关组织是否与癫痫发作自由相关。因此，我们将确定脑磁图是否是识别HFLV的合适的ECoG的无创性替代品，并验证HFLV的临床重要性。在前瞻性阶段，我们将在符合癫痫手术条件的患者中系统地使用脑磁图和皮层脑电图，并确定哪些HFLV频段(亚型)与致痫区域最相关。在这个预期阶段，我们还将研究手术结果和切除组织的病理学，以更好地了解HFLV的重要性。我们相信，该项目的完成将促进对癫痫发病机制的科学认识，更重要的是，将提高本病患者癫痫手术的疗效。 与公共卫生相关：定位导致癫痫发作的脑组织具有挑战性，但可能导致手术减少-甚至消除-癫痫患者的癫痫发作。为了帮助识别这种组织，我们将研究大脑中的高频低压电活动，它在引发癫痫发作中的重要性直到最近才被认识到。我们将使用有创(皮质脑电图术)和非侵入性(脑磁图)技术来识别这种活动，并确定它的存在和位置是否影响癫痫手术的成功。

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.