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，持续5-10秒的凝视，与脑电图（EEG）上的节律性“棘波”放电（SWD）相关。尽管被认为是全身性癫痫的一种形式，但人类和动物的EEG记录都表明SWD涉及选择性皮质和皮质下网络，同时保留其他区域。我们的中心假设是，在特定的网络中增加神经元放电导致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被选择性地参与，以及SWD期间这些脑区的神经元活动是否增加或减少。以前的研究未能充分解决这个问题。虽然功能性磁共振成像（fMRI）已成为神经科学研究中的常用工具，但在此，我们将联合收割机与其他神经成像和局部生理学方法相结合，以增强数据解释。使用已建立的啮齿动物癫痫模型，我们将首先通过同步，共定位电生理和光纤脑血流量（CBF）和血氧分压记录在SWD神经元活动的神经影像信号。 我们最近校准了血氧水平依赖性（BOLD）fMRt;分别测量fMRI，CBF和脑血容量（CBV），以获得脑氧代谢率（CMRO 2）的定量图，这是一种更直接的神经元活动测量方法。因此，我们接下来将通过校准的BOLD在SWD期间获得高空间分辨率的CMRO 2图。最后，我们将研究动态变化，通过高时间分辨率脑电触发功能磁共振成像在SWD。了解棘波癫痫发作涉及的特定区域网络，以及神经元活动是否增加或减少，可能最终导致这些区域的靶向治疗，包括基因治疗，选择性药物或深部脑刺激。在这种良好表征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.