Characterizing Sleep Signatures and its effects on Cognition in New-Onset Temporal Lobe Epilepsy

新发颞叶癫痫的睡眠特征及其对认知的影响

• 批准号: 10644795
• 负责人: Temitayo Oyegbile-Chidi
• 金额: $ 19.26万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644795
• 关键词: Academy; Acoustic Stimulation; Address; Adult; Anticonvulsants; Attention; Attentional deficit; Award; Behavior; Biological Markers; Childhood; Chronic; Clinical Trials Design; Cognition; Cognitive; Cognitive deficits; Coupled; Coupling; Crossover Design; Data; Development; Disease; Elderly; Electroencephalography; Epilepsy; Exhibits; Functional Magnetic Resonance Imaging; Goals; Impairment; Individual; Interruption; Intervention; Intervention Trial; Knowledge; Learning; Link; Measures; Medicine; Memory; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Mentors; Monitor; National Institute of Neurological Disorders and Stroke; Newly Diagnosed; Participant; Patients; Pattern; Performance; Persons; Pharmaceutical Preparations; Phase; Physicians; Polysomnography; Public Health; Quality of life; Randomized; Research; Research Priority; Scalp structure; Schools; Scientist; Seizures; Sleep; Sleep Architecture; Sleep Disorders; Sleep Fragmentations; Sleep disturbances; Techniques; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Therapeutic Intervention; Time; Training; Underemployment; United States; cognitive development; cognitive enhancement; cognitive function; cognitive performance; comorbidity; comparison control; density; epileptiform; experience; high risk; improved; low socioeconomic status; memory consolidation; memory recall; neural network; non rapid eye movement; novel; poor sleep; skills; sleep abnormalities; sleep pattern; sleep physiology; sleep spindle; sustained attention; young adult

Project Summary/Abstract Temporal Lobe Epilepsy (TLE) is characterized by disordered neural network activity and temporal lobe seizures. As many as 3 million individuals with TLE in the United States also experience cognitive and sleep problems, resulting in poor school performance in childhood, with high risk of underemployment in adulthood, and consequent lower socioeconomic status. Individuals with TLE frequently experience sleep fragmentation, which disrupts memory consolidation and sustained attention, both of which are impaired in this disorder. While these comorbidities can be long-term consequences of repeated seizures and medications, it is now known that they also often present prior to the first recognized seizure and worsen over time even with successful seizure treatment. This suggests that an early neural network abnormality may underlie seizure development while simultaneously impairing sleep and cognitive development, even prior to the added effects of disorder chronicity. In spite of this, there has been limited research addressing mechanisms underlying these sleep and cognitive problems in TLE. This represents a critical unmet public health need and both the National Academy of Medicine and NINDS have identified this notable gap as a research priority. I will begin to address this gap with the my K23 proposal by investigating abnormal sleep architecture patterns in TLE that directly contribute to cognitive deficits using both an observational (Aim 1) and a mechanistic interventional (Aim 2) approach. In typical NREM sleep, electroencephalogram (EEG) slow wave oscillations are phase-locked and coupled with sleep spindle oscillations (SW-SSO), which facilitates memory consolidation and potentially improves attention. In TLE, disordered networks that result in interictal epileptic discharges and seizures may also contribute to altered SW-SSO coupling during sleep, resulting in memory and attention deficits. A single night of acoustic stimulation (AS) has been proven effective in enhancing SW-SSO coupling and improving cognitive performance in healthy older adults but has not been studied in TLE. My central hypothesis is that disordered networks in newly diagnosed TLE patients result in altered sleep architecture, which disrupt memory consolidation and attention capability. I will test this hypothesis by: (1) characterizing TLE sleep architecture using computational EEG – sleep spindle density, slow wave power, interictal epileptiform discharges, and SW-SSO coupling (Aim 1a), (2) linking these specific TLE-related sleep architecture patterns to cognitive processing (Aim 1b); (3) determining if AS enhances SW-SSO coupling in young adults with TLE (Aim 2a) and (4) determining if enhanced SW-SSO coupling improves memory and attention in TLE (Aim 2b). This training award will provide me the opportunity to extend my research expertise into computational sleep EEG acquisition and analysis, acoustic stimulation techniques, and clinical trial design. My long-term goal is to leverage connections between sleep, behavior and neural network activity to develop and implement tailored cognitive and sleep interventions for individuals with epilepsy.

项目概要/摘要 颞叶癫痫 (TLE) 的特点是神经网络活动紊乱和颞叶癫痫发作。 在美国，有多达 300 万 TLE 患者也存在认知和睡眠问题， 导致儿童时期学业成绩不佳，成年后就业不足的风险很高，以及 随之而来的社会经济地位较低。患有 TLE 的人经常会经历睡眠碎片化，这 扰乱记忆巩固和持续注意力，这两者在这种疾病中都会受到损害。虽然这些 合并症可能是反复癫痫发作和药物治疗的长期后果，现在已知它们 也经常在第一次确认癫痫发作之前出现，并且即使癫痫发作成功，也会随着时间的推移而恶化 治疗。这表明早期神经网络异常可能是癫痫发作的基础，而 同时损害睡眠和认知发展，甚至先于慢性疾病的额外影响。 尽管如此，针对这些睡眠和认知背后的机制的研究仍然有限。 TLE 中的问题。这代表了一个关键的未满足的公共卫生需求，美国国家科学院 医学和 NINDS 已将这一显着差距确定为研究重点。我将开始解决这个差距 我的 K23 提案通过调查 TLE 中的异常睡眠架构模式来直接导致 使用观察（目标 1）和机械干预（目标 2）方法来治疗认知缺陷。在 典型的 NREM 睡眠、脑电图 (EEG) 慢波振荡是锁相的并与 睡眠纺锤波振荡（SW-SSO），有助于记忆巩固并可能提高注意力。 在 TLE 中，导致发作间期癫痫放电和癫痫发作的紊乱网络也可能导致 睡眠期间 SW-SSO 耦合发生改变，导致记忆力和注意力缺陷。一个晚上的声学 刺激 (AS) 已被证明可有效增强 SW-SSO 耦合并提高认知能力 健康老年人中存在这种情况，但尚未在 TLE 中进行研究。我的中心假设是，无序的网络 新诊断的 TLE 患者会导致睡眠结构改变，从而破坏记忆巩固和 注意力能力。我将通过以下方式测试这个假设：(1) 使用计算来表征 TLE 睡眠架构 EEG – 睡眠纺锤体密度、慢波功率、发作间期癫痫样放电和 SW-SSO 耦合（目标 1a)、(2) 将这些特定的 TLE 相关睡眠结构模式与认知处理联系起来（目标 1b）； (3) 确定 AS 是否增强 TLE 年轻人的 SW-SSO 耦合（目标 2a）和 (4) 确定是否增强 SW-SSO 耦合可改善 TLE 中的记忆力和注意力（目标 2b）。这个培训奖将为我提供 有机会将我的研究专业知识扩展到计算睡眠脑电图采集和分析、声学 刺激技术和临床试验设计。我的长期目标是利用睡眠之间的联系， 行为和神经网络活动，以开发和实施量身定制的认知和睡眠干预措施 患有癫痫症的人。