Relating Vigilance to Connectivity and Neurocognition in Temporal Lobe Epilepsy

将警惕性与颞叶癫痫的连通性和神经认知联系起来

• 批准号: 10618398
• 负责人: Catherine Elizabeth Chang
• 金额: $ 57.26万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618398
• 关键词: Address; Affect; Amygdaloid structure; Antiepileptic Agents; Area; Atrophic; Attention; Behavior; Behavior Therapy; Biomedical Research; Brain; Clinical; Clinical Treatment; Cognition; Cognitive; Cognitive deficits; Communities; Conscious; Data; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Drowsiness; Early treatment; Electroencephalography; Epilepsy; Evaluation; Excessive Daytime Sleepiness; Executive Dysfunction; Eye; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Hippocampus; Human; Imaging Techniques; Impaired cognition; Impairment; Individual; Investigation; Left; Location; Magnetic Resonance Imaging; Measures; Mediating; Medical; Memory Loss; Metabolism; Modeling; Multimodal Imaging; Neocortex; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neuropsychology; Operative Surgical Procedures; Patients; Pattern; Pharmaceutical Preparations; Play; Population; Quality of life; Questionnaires; Recurrence; Refractory; Regulation; Rodent; Role; Seizures; Source; Speed; Structure; System; Techniques; Temporal Lobe; Temporal Lobe Epilepsy; Thalamic structure; Therapeutic Intervention; Work; basal forebrain; executive function; gray matter; imaging modality; improved; multimodality; neocortical; nervous system disorder; network dysfunction; neural; neural stimulation; neuroimaging; neuroregulation; novel; novel strategies; prevent; processing speed; sustained attention; verbal; vigilance

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.

项目总结/摘要 颞叶癫痫（TLE）是一种破坏性的和常见的神经系统疾病，其中患者患有 频繁的意识损害癫痫发作、广泛的神经认知缺陷和生活质量下降。给定 癫痫发作起源于海马体或杏仁核，为什么TLE患者表现出认知功能 与颞叶功能无关的缺陷-如执行功能下降，认知处理 速度和注意力-以及新皮层代谢和功能连接的弥漫性下降？ 鉴于先前观察到TLE的警惕性降低，癫痫发作可能会破坏活动和长期- 范围连接皮层下的大脑结构参与警觉调节，我们提出，皮层下， 激活潜在的警觉性网络在介导广泛的神经和认知过程中起着关键作用。 局灶性TLE的影响。具体来说，我们的中心假设是， TLE可能导致皮层下警觉中心和皮层之间的功能连接障碍， 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，我们计划进行人类神经成像研究， 大脑连接（目标1），认知到警觉（目标2），以及连接到认知（目标3）。在目标1中，我们 使用同步fMRI-EEG表征健康对照中的警觉依赖性功能连接， 这将指导选择皮质下-皮质连接以探测患者（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戒措施相关联，使用完整的 神经心理学评估和心理速度和过度嗜睡的评估， 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 测量患者与对照组的皮质下-皮质连接（重点关注目标1中未覆盖的区域）， 研究皮层下激活结构的长程连接在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。使用这种新颖的方法， 多模式成像与深入的神经认知评估，我们希望确定警惕中心 TLE中的连接扰动影响警觉状态并可能导致神经认知下降。 这项工作可能有助于揭示皮质下神经调节靶点，并建议需要早期手术治疗。 干预和行为疗法来治疗这种毁灭性的疾病。