Neural correlates of impaired consciousness in childhood absence epilepsy

描述（由申请人提供）：儿童期缺失性癫痫（CAE）是一种普遍形式的癫痫，引起短暂的意识障碍。然而，癫痫发作期间的这种损害不是全有或全无的现象，而是不同程度地影响患者的任务表现。在脑电图（EEG）上，失神癫痫表现为3-4赫兹的峰波放电，并在功能磁共振成像（fMRI）上显示脑区血氧变化的时间过程。目前尚不清楚失神发作是如何引起患者意识的可变损伤的。初步数据表明，在癫痫发作间隙的缺席性癫痫中，包括内侧额叶皮质/前扣带（MFC/ACC）和双侧脑岛在内的注意网络区域受到选择性影响。我们的中心假设是，失神癫痫会影响癫痫发作期间的注意网络区域，从而不同程度地损害行为。我们计划通过同时记录儿童CAE患者在失神发作期间的行为、脑电图和功能磁共振成像来研究癫痫发作期间行为波动的潜在神经基础。我们的第一个目标是通过两种需要不同程度的注意力警觉性的连续任务来描述癫痫发作期间的行为。任务表现将被用来分类癫痫发作是与良好或受损的行为和表现在时间的时代在癫痫发作的过程中进行比较。我们的第二个目标是将EEG变化与目标1中发现的可变任务表现联系起来。先前与注意力相关的3-4 Hz和高频伽马波段的脑电图功率，以及与不同大脑状态相关的100 ms原型脑电图地形，将与任务表现相关。我们的第三个目标是通过分析中脑皮层/前扣带和双侧岛的时间过程和网络连通性，将行为与fMRI信号的变化联系起来。新皮质功能受损和认知缺陷显著降低CAE患者的生活质量。了解局灶性癫痫可变行为的基本机制可能会改善这种疾病的靶向治疗。

DESCRIPTION (provided by applicant): Childhood absence epilepsy (CAE) is a generalized form of epilepsy causing transitory impairments of consciousness. However, this impairment during seizures is not an all-or-nothing phenomenon but variably affects task performance in patients. Absence seizures are seen as 3-4 Hz spike-and-wave discharges on electroencephalography (EEG) and cause a time course of blood oxygenation changes in brain areas seen in functional magnetic resonance imaging (fMRI). It is unknown how absence seizures cause variable impairments of consciousness in patients. Preliminary data suggests that attention network areas including the medial frontal cortex/anterior cingulate (MFC/ACC) and bilateral insula are selectively affected in absence epilepsy between seizures. Our central hypothesis is that absence epilepsy affects attention network areas during seizures to variably impair behavior. We plan to investigate the underlying neural basis of fluctuations in behavior during seizures through simultaneous behavioral, EEG, and fMRI recordings in pediatric CAE patients during absence seizures. Our first aim will be to characterize behavior during seizures using two tasks of continuous performance over time, which require different levels of attentional vigilance. Task performance will be used to categorize seizures as being associated with good or impaired behavior and performance in epochs of time over the course of seizures will be compared. Our second aim is to relate EEG changes with the variable task performance found in Aim 1. EEG power at the 3-4 Hz and high frequency gamma bands previously associated with attention, as well as prototypical 100 ms EEG topographies associated with distinct brain states, will be correlated with task performance. Our third aim is to relate behavior to changes in fMRI signals by analyzing the time course and network connectivity of the MCC/ACC and bilateral insula. Impaired neocortical function and cognitive deficits significantly reduce the quality of life in patients with CAE. Understanding the fundamental mechanisms of variable behavior in focal epilepsy may lead to improved, targeted therapies for this disorder.