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.

项目总结/摘要 颞叶癫痫（Temporal Lobe Epilepsy，TLE）是一种以神经网络活动紊乱和颞叶癫痫发作为特征的疾病。 在美国，多达300万TLE患者也会出现认知和睡眠问题， 导致儿童时期学习成绩差，成年后就业不足的风险高， 社会经济地位较低。TLE患者经常经历睡眠碎片，这 破坏记忆巩固和持续注意力，这两者在这种疾病中都受到损害。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， 也经常出现在第一次癫痫发作之前，并随着时间的推移而恶化，即使癫痫发作成功 治疗这表明早期神经网络异常可能是癫痫发作的基础， 同时损害睡眠和认知发展，甚至在慢性疾病的附加影响之前。 尽管如此，关于这些睡眠和认知障碍的潜在机制的研究仍然有限。 问题在TLE这代表了一个关键的未满足的公共卫生需求， 医学和NINDS已将这一显著差距确定为研究重点。我将开始解决这一差距， 我的K23建议通过调查TLE中的异常睡眠结构模式， 使用观察（目标1）和机械干预（目标2）方法治疗认知缺陷。在 在典型的NREM睡眠中，脑电图（EEG）慢波振荡是锁相的并且与 睡眠纺锤波振荡（SW-SSO），这有助于记忆巩固，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有助于 睡眠期间改变SW-SSO偶联，导致记忆和注意力缺陷。一个晚上的声学 刺激（AS）已被证明在增强SW-SSO耦合和改善认知表现方面是有效的 在健康的老年人中，但尚未在TLE中进行研究。我的中心假设是， 新诊断的TLE患者会导致睡眠结构改变，从而破坏记忆巩固， 注意力能力。我将测试这一假设：（1）表征TLE睡眠结构使用计算 EEG -睡眠梭形密度、慢波功率、发作间期癫痫样放电和SW-SSO耦合（目的 （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是否增强了年轻TLE成年人的SW-SSO偶联（Aim 2a），以及（4）确定AS是否增强了TLE成年人的SW-SSO偶联（Aim 2a）， SW-SSO偶联改善TLE的记忆和注意力（目标2b）。这个培训奖将为我提供 有机会将我的研究专长扩展到计算睡眠EEG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和睡眠之间的联系， 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， 癫痫病患者。