Neural correlates of impaired consciousness in childhood absence epilepsy

描述（由申请人提供）：儿童失神性癫痫（CAE）是一种全身性癫痫，引起短暂的意识障碍。然而，癫痫发作期间的这种损害不是一种全有或全无的现象，而是会影响患者的任务表现。失神发作在脑电图（EEG）上表现为3-4 Hz的棘波放电，并在功能性磁共振成像（fMRI）中观察到大脑区域的血氧变化。目前尚不清楚失神发作如何导致患者的意识障碍。初步数据表明，注意网络区域，包括内侧额叶皮层/前扣带回（MFC/ACC）和双侧颞叶癫痫发作之间的失神癫痫选择性地受到影响。我们的中心假设是失神癫痫在发作期间影响注意力网络区域，从而损害行为。我们计划通过同步行为、EEG和fMRI记录来研究儿童CAE患者失神发作期间行为波动的潜在神经基础。我们的第一个目标将是表征癫痫发作期间的行为，使用两个任务的连续性能随着时间的推移，这需要不同水平的注意力警惕。任务表现将用于将癫痫发作分类为与良好或受损行为相关，并将比较癫痫发作过程中不同时间段的表现。我们的第二个目标是将EEG变化与目标1中发现的可变任务性能联系起来。先前与注意力相关的3-4 Hz和高频伽马波段的EEG功率，以及与不同大脑状态相关的原型100 ms EEG地形图，将与任务表现相关。我们的第三个目标是通过分析MCC/ACC和双侧大脑皮层的时间进程和网络连接，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。了解局灶性癫痫中可变行为的基本机制可能会导致这种疾病的改进，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.