Neuroimaging, energetics, and neuronal activity in spike-wave seizures

描述(由申请人提供)： 失神癫痫是一种常见的儿童癫痫发作障碍，与5-10秒的无反应发作有关，这可能对儿童的学习成绩和心理社会互动产生不利影响。在EEG上，失神发作的特征是有节奏的“棘波”放电(SWD)，很可能是由皮质丘脑神经元网络产生的。虽然失神发作被经典地认为是全身性癫痫事件，但最近的研究表明，大脑局部区域受累，而其他区域未受影响。我们的中心假设是，特定的皮质和皮质下网络参与了SWD，与基线相比，一些区域显示出神经元活动增加，而另一些区域显示出活动减少。 功能神经成像有可能在整个大脑中无创地绘制出SWD期间局部活动的变化。以前的神经成像研究已经确定了fMRI信号和神经元活动之间的密切关系。然而，神经成像具有有限的时空分辨率，并且仅与神经元活动间接相关。这些局限性可以通过将fMRI信号与局部能量学联系起来，然后直接将能量学与神经元活动联系起来来克服。因此，为了准确地描述与棘波发作相关的大脑区域，我们提出了一种在大鼠模型中进行SWD的多模式研究，使用跨越广泛时空领域的技术。我们的具体目标是：1)使用功能磁共振成像绘制SWD涉及的皮质和皮质下网络；2)测量SWD过程中的血管反应并计算神经能量学，将成像信号与神经元活动联系起来；3)直接测量SWD过程中相关脑区的电生理变化。这种神经成像和电生理技术的结合将使我们能够清楚地描述SWD期间整个大脑神经活动的变化，从而能够全面描述这些癫痫发作所涉及的网络。我们预计会发现区域的异质性，在SWD期间，某些区域的神经元活性增加，一些区域的神经元活动减少，而其他区域则较少。了解哪些皮质和皮质下网络参与了SWD，将指导未来失神癫痫局部病理生理学的研究，并可能导致靶向治疗的发展。 公共卫生相关性：失神发作影响17%的癫痫儿童，并与凝视发作有关，后者对儿童的学习成绩和社交活动产生负面影响。更好地了解失神发作的机制和了解哪些脑区参与可能会导致更好地治疗失神癫痫和其他相关的癫痫发作障碍。

DESCRIPTION (provided by applicant): Absence epilepsy is a common seizure disorder in children, associated with 5-10 second episodes of unresponsiveness that can adversely affect a child's academic performance and psychosocial interactions. On EEG, absence seizures are characterized by rhythmic "spike-wave" discharges (SWD), likely generated by corticothalamic neuronal networks. Although absence seizures are classically considered generalized epileptic events, recent studies suggest that focal brain regions are involved while other areas are spared. Our central hypothesis is that specific cortical and subcortical networks are involved in SWD, with some regions displaying increased neuronal activity and others showing decreased activity compared to baseline. Functional neuroimaging has the potential to map regional activity changes during SWD noninvasively throughout the brain. Previous neuroimaging studies have established a strong relationship between fMRI signals and neuronal activity. However, neuroimaging has limited spatiotemporal resolution and is only indirectly related to neuronal activity. These limitations can be overcome by associating fMRI signals with localized energetics and then directly connecting energetics to neuronal activity. Therefore, to accurately characterize the brain regions involved in spike-wave seizures, we propose a multimodal study of SWD in a rat model, using techniques spanning a wide range of spatiotemporal domains. Our specific aims are: 1) To map the cortical and subcortical networks involved in SWD using fMRI, 2) To measure vascular responses and calculate neuroenergetics during SWD, relating imaging signals to neuronal activity, and 3) To directly measure electrophysiological changes during SWD within involved brain regions. This combination of neuroimaging and electrophysiological techniques will allow unambiguous description of changes in neuronal activity throughout the brain during SWD, allowing a comprehensive characterization of the networks involved in these seizures. We expect to find regional heterogeneity, with certain regions showing increases in neuronal activity during SWD, some showing decreases, and sparing of other areas. Knowledge of which cortical and subcortical networks are involved in SWD will guide future studies into the local pathophysiology of absence epilepsy and may lead to the development of targeted treatments. Public Health Relevance: Absence seizures affect 17% of children with epilepsy, and are associated with staring spells that negatively impact a child's school performance and social interactions. A better understanding of the mechanisms of absence seizures and knowledge of which brain regions are involved may lead to better treatments for absence epilepsy and other related seizure disorders.