Neuronal firing and neuroimaging in spike-wave seizures

描述（由申请人提供）：失神发作最常见于儿童，表现为持续5-10秒的凝视，伴有脑电图（EEG）上有节奏的“尖波”放电（SWD）。虽然被认为是一种全身性癫痫，但人类和动物的脑电图记录表明，SWD涉及选择性皮质和皮质下网络，而不涉及其他区域。我们的中心假设是，特定网络中神经元放电的增加导致了SWD的区域异质性。由于这可能具有重要的治疗意义，我们的主要目标是确定哪些特定的解剖网络选择性参与，以及在SWD期间这些大脑区域的神经元活动是增加还是减少。以往的研究未能充分解决这一问题。虽然功能磁共振成像（fMRI）已成为神经科学研究的常用工具，但在这里，我们将fMRI与其他神经成像和局部生理学方法结合起来，以增强数据解释。利用已建立的啮齿动物癫痫模型，我们将首先通过同时、共定位的电生理和光纤脑血流量（CBF）和pO2记录将神经元活动与神经成像信号联系起来。我们最近校准了血氧水平依赖（BOLD） fMRt；分别测量功能磁共振成像（fMRI）、脑血流（CBF）和脑血容量（CBV），获得脑氧代谢率（cro2）的定量图，这是神经元活动的一种更直接的测量方法。因此，我们接下来将通过校准的BOLD获得SWD期间的高空间分辨率cmor2地图。最后，我们将通过高时间分辨率脑电图触发功能磁共振成像研究SWD期间的动态变化。了解与尖波发作有关的特定区域网络，以及神经元活动是否增加或减少，可能最终导致对这些区域的靶向治疗，包括基因治疗、选择性药理学药物或深部脑刺激。在这个特征良好的模型中使用的方法也可以增强解释人类非侵入性癫痫神经影像学研究的能力。

DESCRIPTION (provided by applicant): Absence seizures occur most commonly in children as staring spells lasting 5-10 seconds, associated with a rhythmic "spike-wave" discharge (SWD) on electroencephalography (EEG). Although considered a form of generalized epilepsy, both human and animal EEG recordings suggest that SWD involve selective cortical and subcortical networks, while sparing other regions. Our central hypothesis is that increased neuronal firing in specific networks leads to regional heterogeneity in SWD. Since this may have important therapeutic significance, our main goal is to determine which specific anatomical networks are selectively involved, and whether neuronal activity during SWD increases or decreases in these brain regions. Previous studies have failed to adequately address this problem. While functional MRI (fMRI) has become a common tool in neuroscience research, here we will combine fMRI with other neuroimaging and local physiology methods to enhance data interpretation. Using an established rodent epilepsy model, we will first relate neuronal activity to neuroimaging signals through simultaneous, co-localized electrophysiology and fiber optic cerebral blood flow (CBF) and pO2 recordings during SWD. We recently calibrated blood oxygen level dependent (BOLD) fMRt; separately measuring fMRI, CBF and cerebral blood volume (CBV) to obtain quantitative maps of the cerebral metabolic rate of oxygen (CMRO2), a more direct measure of neuronal activity. Therefore, we will next obtain high spatial resolution CMRO2 maps during SWD through calibrated BOLD. Finally, we will study dynamic changes through high temporal resolution EEG-triggered fMRI during SWD. Knowledge of the specific regional networks involved in spike-wave seizures, and whether increases or decreases in neuronal activity occur, may lead ultimately to targeted treatment in these regions including gene therapy, selective )harmacological agents, or deep brain stimulation. The approach used in this well-characterized model may also enhance the ability to interpret noninvasive epilepsy neuroimaging studies in humans.