WORKING MEMORY IN OBSTRUCTIVE SLEEP APNEA-AN fMRI STUDY

阻塞性睡眠呼吸暂停中的工作记忆——功能磁共振成像研究

• 批准号: 7120071
• 负责人: Robert Joseph Thomas
• 金额: $ 15.17万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120071
• 关键词: behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; clinical research; functional magnetic resonance imaging; human subject; hypoxia; neural information processing; neuropsychological tests; patient oriented research; polysomnography; respiratory airflow disorder; short term memory; sleep apnea; sleep deprivation

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is associated with abnormalities of higher order executive cognitive functions. The precise neuroanatomical localization of these deficits is unknown. The physiological correlates of executive cognitive dysfunction are poorly defined, and recovery following therapy may be incomplete. This project proposes the novel use of a neuroimaging technology, functional magnetic resonance imaging (fMRI), and precise neurobehavioral protocols, to localize the neuroanatomical site of dysfunction. Additional protocols will isolate specific physiological correlates of these neurocognitive abnormalities such as sleep fragmentation, sleep deprivation, and nocturnal oxygen desaturation and will relate them to altered regional cortical function. We will examine the cause of incomplete recovery of executive function while on therapy with nasal positive airway pressure. Working memory is a brain system that provides temporary storage and manipulation of information necessary to execute complex cognitive tasks, and it contributes to several executive functions. The n-back paradigm is an extensively used probe of working memory in MU studies, and is normally associated with activation of dorsolateral prefrontal cortex (DLPFC), anterior cingulate and posterior parietal cortex. We have adapted this task at the 2- back level of difficulty for use in OSA patients. Our preliminary data suggest a reversible (with treatment) reduction of working memory capacity in OSA patients that may be secondary to selective dysfunction in the DLPFC, relative to other nodes in the executive control network. Based on this data we hypothesize that: 1) Patients with OSA have reduced activation of the DLPFC, relative to posterior parietal cortex during tests of working memory. 2) Sleep deprivation or fragmentation but not nocturnal hypoxia disrupts working memory in normal subjects. 3). Post-treatment residual abnormalities are caused by persisting sleep fragmentation, not prior hypoxic exposure. The P.I. has training in general medicine, neurology, sleep disorders and functional neuroimaging. The proposed projects will be performed under the direct guidance of experts in sleep disorders, cognitive neuroscience, and fMRI within the Harvard system. The relevant research environment is particularly rich at the participating institutions-basic and applied neurobiology of sleep, clinical sleep disorders, behavioral neurology, and fMRI. The career development plan will include training in MRI physics, applied MRI, statistics and research methodology, ethics, planning of clinical research, and cognitive neuroscience. The immediate career goal is to acquire the necessary skills for applied clinical fMRI and determine the functional neurocircuitry of the localization, etiology and recovery of reduced working memory capacity in patients with OSA using the 2-back task paradigm. The longterm career goal is to develop a model of the function of sleep by demonstrating the functional consequences of sleep disruption in conditions such as depression, age-related memory dysfunction, and attention deficit hyperactivity disorder.

描述（由申请人提供）： 阻塞性睡眠呼吸暂停（OSA）与高阶的异常有关 执行认知功能。精确的神经解剖学定位 这些缺陷尚不清楚。执行认知的生理相关性 功能障碍的定义较差，治疗后的恢复可能是 不完整。该项目提出了一种新颖的神经影像技术的使用， 功能性磁共振成像（fMRI）和精确的神经行为 协议，定位功能障碍的神经解剖部位。额外的 协议将隔离这些特定的生理相关性 神经认知异常，例如睡眠破碎，睡眠剥夺， 和夜间氧气去饱和，并将它们与改变的区域联系起来 皮质功能。我们将检查不完整恢复的原因 执行功能在鼻腔阳性气道压力下进行治疗。 工作记忆是一个提供临时存储和的大脑系统 操纵执行复杂认知任务所需的信息，并 它有助于几个执行职能。 n背范式是 在MU研究中广泛使用了工作记忆的探针，通常是 与前外侧前额叶皮层（DLPFC）的激活相关，前部 扣带和后顶叶皮层。我们已经在2-中调整了这项任务 在OSA患者中使用难度的后水平。我们的初步数据暗示 可逆（处理）降低OSA的工作记忆能力 可能继发于DLPFC中选择性功能障碍的患者相对 到执行控制网络中的其他节点。基于这些数据，我们 假设：1）OSA患者的DLPFC激活降低， 在工作记忆测试期间，相对于后顶叶皮层。 2）睡觉 剥夺或分散化，但夜间缺氧不会破坏工作记忆 在正常受试者中。 3）。治疗后残留异常是由 持续的睡眠破碎，而不是先前的低氧暴露。 P.I.接受通用医学，神经病学，睡眠障碍和 功能性神经影像学。拟议的项目将在 睡眠障碍，认知神经科学和专家的直接指导 哈佛系统中的fMRI。相关的研究环境是 在参与机构的基础上特别丰富 睡眠的神经生物学，临床睡眠障碍，行为神经病学和 fMRI。职业发展计划将包括MRI物理学培训， 应用的MRI，统计和研究方法，伦理，临床规划 研究和认知神经科学。直接的职业目标是获得 应用临床fMRI的必要技能并确定功能 定位，病因和恢复工作减少的神经循环 OSA患者使用2折叠任务范式的记忆力。长期 职业目标是建立一个模型的睡眠功能 证明条件下睡眠破坏的功能后果 例如抑郁症，与年龄相关的记忆功能障碍和注意力不足 多动症障碍。