Relating Vigilance to Connectivity and Neurocognition in Temporal Lobe Epilepsy

项目摘要/摘要 摘要颞叶癫痫(TLE)是一种严重且常见的神经系统疾病。 频繁出现意识受损的癫痫发作，广泛的神经认知缺陷，以及生活质量下降。vt.给出 癫痫发作起源于海马体或杏仁核，为什么TLE患者表现出认知能力 与颞叶功能无关的缺陷--例如执行功能下降、认知处理能力下降 速度和注意力--以及新皮质新陈代谢和功能连接的弥漫性下降？ 鉴于先前观察到的TLE警觉水平降低，以及癫痫发作可能扰乱活动和长时间... 参与警觉调节的皮质下大脑结构的范围连通性，我们认为皮质下 激活警觉下的网络在调节广泛的神经和认知过程中起着关键作用 焦点TLE的影响。具体地说，我们的中心假设是反复发作的意识受损的癫痫在 TLE可能导致皮质下警觉中心和皮质之间的功能连接障碍，导致 警觉状态的损害可能导致无法用时间解释的神经认知问题 肺叶功能障碍。为了解决这一假设，我们计划进行与警觉相关的人类神经成像研究 大脑连接(目标1)、认知到警觉(目标2)和认知连接(目标3)。在目标1中，我们将 用同步fMRI-EEG研究健康人警觉性依赖的功能连接性， 这将指导选择皮质下-皮质连接以探查患者(目标3)。在目标2中，我们将 将个体神经认知参数与患者和对照组的警觉措施联系起来，使用完整的 神经心理学评估和精神运动速度和嗜睡过度的评估，以 确定患者的哪些认知缺陷与警觉性受损有关。在目标3中，我们将比较MRI 患者与对照组皮质下-皮质连通性的测量(重点关注目标1中未涉及的区域) 研究大脑皮质下激活结构的长距离连接在TLE中是如何受到干扰的，我们将 将这些连接障碍与神经认知缺陷联系起来。使用这种新的方法，将 多模式成像结合深入的神经认知评估，我们预计将确定警觉中心 TLE中的连接性干扰会影响警觉状态，并可能导致神经认知功能下降。 这项工作可能有助于发现皮质下神经调节靶点，并建议有必要进行早期手术 对这一破坏性疾病的干预和行为治疗。

PROJECT SUMMARY/ABSTRACT Temporal lobe epilepsy (TLE) is a devastating and common neurological disorder in which patients suffer from frequent consciousness-impairing seizures, broad neurocognitive deficits, and diminished quality of life. Given that seizures originate focally in the hippocampus or amygdala, why do TLE patients demonstrate cognitive deficits not associated with temporal lobe function – such as decline in executive function, cognitive processing speed, and attention – as well as diffuse decreases in neocortical metabolism and functional connectivity? Given prior observations of reduced vigilance levels in TLE, and that seizures may disrupt the activity and long- range connectivity of subcortical brain structures involved in vigilance regulation, we propose that subcortical activating networks underlying vigilance play a critical role in mediating the widespread neural and cognitive effects of focal TLE. Specifically, our central hypothesis is that recurrent consciousness-impairing seizures in TLE may lead to functional connectivity disturbances between subcortical vigilance centers and cortex, leading to impairments in vigilance state that may contribute to neurocognitive problems not explained by temporal lobe dysfunction. To address this hypothesis, we plan human neuroimaging studies that relate vigilance to brain connectivity (Aim 1), cognition to vigilance (Aim 2), and connectivity to cognition (Aim 3). In Aim 1, we will characterize vigilance-dependent functional connectivity in healthy controls using simultaneous fMRI-EEG, which will guide the selection of subcortical-cortical connections to probe in patients (Aim 3). In Aim 2, we will relate individual neurocognitive parameters to vigilance measures in patients and controls, using a full neuropsychological evaluation and assessments of psychomotor speed and excessive sleepiness, to determine which cognitive deficits in patients are related to impaired vigilance. In Aim 3, we will compare MRI measures of subcortical-cortical connectivity in patients vs. controls (focusing on areas uncovered in Aim 1) to examine how long-range connections from subcortical activating structures are perturbed in TLE, and we will relate these connectivity disturbances to neurocognitive deficits. Using this novel approach that integrates multi-modal imaging with in-depth neurocognitive assessments, we expect to identify vigilance center connectivity perturbations in TLE that influence vigilance state and may contribute to neurocognitive decline. This work may help uncover subcortical neuromodulation targets and suggest the need for earlier surgical intervention and behavioral therapies in this devastating disorder.