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.

项目摘要/摘要 颞叶癫痫（TLE）的特征是神经网络活性和暂时瓣癫痫发作。 在美国，多达300万人患有TLE的人也经历了认知和睡眠问题， 导致童年的学校表现不佳，成年后的就业不足的风险很高，并且 因此，社会经济地位较低。患有TLE的人经常经历睡眠破碎化，这是 破坏记忆巩固并持续关注，这两者在这种疾病中受到损害。而这些 合并症可能是反复癫痫发作和药物的长期后果，现在知道他们 也经常在第一次公认的癫痫发作之前出现，即使成功癫痫发作，随着时间的流逝也更糟 治疗。这表明早期的神经网络异常可能是癫痫发育的基础 同时损害睡眠和认知发展，甚至在疾病慢性的增加之前。 尽管如此，仍有有限的研究解决了这些睡眠和认知的基础机制 TLE中的问题。这代表了未满足的公共卫生需求和美国国家学院 医学和Ninds已将这一显着差距确定为研究的重点。我将开始解决这个差距 我的K23提案通过调查TLE中的异常睡眠结构模式直接有助于 使用观察性（AIM 1）和机械介入（AIM 2）方法的认知缺陷。 典型的NREM睡眠，脑电图（EEG）慢波振荡是相锁的，并与 睡眠主轴振荡（SW-SSO），设施记忆合并并有可能提高注意力。 在TLE中，导致癫痫发作和癫痫发作的无序网络也可能有助于 在睡眠期间改变了SW-SSO耦合，导致记忆力和注意力不足。一夜的声学 刺激（AS）已被证明有效地增强了SW-SSO耦合和改善认知性能 在健康的老年人中，但尚未在TLE中研究。我的中心假设是在 新诊断的TLE患者会导致睡眠结构改变，这破坏了记忆巩固和 注意能力。我将通过：（1）使用计算来表征TLE睡眠体系结构来检验此假设 脑电图 - 睡眠主轴密度，慢波功率，间隔癫痫样放电和SW-SSO耦合（AIM 1a），（2）将这些特定的与TLE相关的睡眠结构模式与认知处理联系起来（AIM 1B）； （3） 确定AS是否增强了TLE（AIM 2A）的年轻人的SW-SSO耦合，并且（4）确定是否增强 SW-SSO耦合可改善TLE中的记忆力和注意力（AIM 2B）。该培训奖将为我提供 将我的研究专业知识扩展到计算睡眠脑电图获取和分析的机会 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 患有癫痫的人。