Neuronal firing and neuroimaging in spike-wave seizures

棘波癫痫发作的神经元放电和神经影像学

• 批准号: 6806788
• 负责人: HAL BLUMENFELD
• 金额: $ 36.05万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806788
• 关键词: bioimaging /biomedical imaging; blood volume; brain circulation; brain electrical activity; brain imaging /visualization /scanning; disease /disorder model; electroencephalography; fiber optics; functional magnetic resonance imaging; generalized seizures; laboratory rat; neural transmission; oxygen consumption

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.

描述（由申请人提供）：缺席癫痫发作最常见于儿童的凝视咒语，持续了5-10秒，与脑电图（EEG）上的节奏“ Spike-Wave”放电（SWD）有关。尽管被认为是一种广义癫痫的形式，但人类和动物的脑电图记录都表明SWD涉及选择性皮质和皮质下网络，同时又涉及其他区域。我们的中心假设是，在特定网络中的神经元触发增加会导致SWD中的区域异质性。由于这可能具有重要的治疗意义，因此我们的主要目标是确定哪些特定的解剖网络有选择性地涉及，以及在SWD期间的神经元活性在这些大脑区域中是否增加还是减少。先前的研究未能充分解决这个问题。尽管功能性MRI（fMRI）已成为神经科学研究中的常见工具，但在这里，我们将将功能磁共振成像与其他神经影像学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，我们将通过同时，共定位的电生理学和光纤脑血流（CBF）和SWD期间的纤维脑血流（CBF）与神经成像信号联系起来。 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），以获得氧气的大脑代谢率（CMRO2）的定量图，这是一种更直接的神经元活性测量。因此，接下来，我们将通过校准粗体在SWD期间获得高空间分辨率CMRO2映射。最后，我们将通过在SWD期间通过高时间分辨率EEG触发的fMRI研究动态变化。了解参与峰波癫痫发作的特定区域网络，以及神经元活性的增加或减少可能导致这些区域的靶向治疗，包括基因疗法，选择性）伤害剂或深脑刺激。在这种良好的模型中使用的方法还可以增强解释人类中非侵袭性癫痫神经影像学研究的能力。