Neural correlates of impaired consciousness in childhood absence epilepsy

描述(申请人提供)：儿童失神癫痫(CAE)是癫痫的一种普遍形式，导致一过性意识障碍。然而，癫痫发作期间的这种损害不是一个要么全有要么全无的现象，而是可变地影响患者的任务表现。失神发作在脑电(EEG)上被认为是3-4赫兹的棘波放电，并在功能磁共振成像(FMRI)中引起脑区血氧变化的一段时间过程。目前尚不清楚失神发作如何导致患者不同程度的意识障碍。初步数据表明，癫痫发作间期失神发作时，注意网络区域包括内侧额叶皮质/扣带前核(MFC/ACC)和双侧脑岛受到选择性影响。我们的中心假设是失神癫痫在癫痫发作期间会影响注意力网络区域，从而以不同的方式损害行为。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。我们的第一个目标将是使用两项随时间连续表现的任务来表征癫痫发作期间的行为，这两项任务需要不同水平的注意警觉。任务表现将被用来将癫痫发作归类为与良好或受损的行为相关，并将比较癫痫发作过程中不同时期的表现。我们的第二个目标是将脑电变化与目标1中发现的可变任务绩效联系起来。先前与注意力相关的3-4赫兹和高频伽马频段的脑电功率，以及与不同大脑状态相关的典型100ms脑电地形图，将与任务绩效相关。我们的第三个目标是通过分析MCC/ACC和双侧脑岛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。了解局灶性癫痫不同行为的基本机制可能会导致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.