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: 6662642
• 负责人: Robert Joseph Thomas
• 金额: $ 15.11万
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6662642
• 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) 与高阶异常相关 执行认知功能。精确的神经解剖学定位 这些赤字是未知的。执行认知的生理相关性 功能障碍的定义不明确，治疗后的恢复可能 不完整。该项目提出了神经成像技术的新颖用途， 功能磁共振成像（fMRI）和精确的神经行为 方案，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，例如睡眠碎片化、睡眠剥夺、 和夜间氧饱和度下降，并将它们与改变的区域联系起来 皮质功能。我们将检查不完全恢复的原因 经鼻气道正压通气治疗时的执行功能。 工作记忆是一个提供临时存储和记忆的大脑系统 处理执行复杂认知任务所需的信息，以及 它有助于实现多种执行功能。 n-back 范式是 MU 研究中广泛使用工作记忆探针，并且通常 与背外侧前额皮质 (DLPFC) 的激活相关 扣带皮层和后顶叶皮层。我们已在 2- OSA 患者的使用难度降低。我们的初步数据表明 OSA 患者工作记忆容量可逆性（通过治疗）减少 可能继发于 DLPFC 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。根据这些数据我们 假设：1) OSA 患者 DLPFC 的激活减少， 在工作记忆测试中相对于后顶叶皮层。 2）睡眠 剥夺或碎片化但夜间缺氧不会扰乱工作记忆 在正常受试者中。 3）。治疗后残留异常的原因是 持续的睡眠碎片化，而不是先前的缺氧暴露。 P.I.接受过普通医学、神经病学、睡眠障碍方面的培训 功能性神经影像学。拟议项目将根据 睡眠障碍、认知神经科学专家的直接指导 哈佛系统内的功能磁共振成像。相关研究环境是 参与机构特别丰富——基础和应用 睡眠神经生物学、临床睡眠障碍、行为神经学和 功能磁共振成像。职业发展计划将包括 MRI 物理学培训， 应用 MRI、统计和研究方法、伦理学、临床规划 研究和认知神经科学。近期的职业目标是获得 应用临床功能磁共振成像的必要技能并确定功能 工作减少的定位、病因和恢复的神经回路 使用 2-back 任务范式评估 OSA 患者的记忆能力。长期来看 职业目标是开发睡眠功能模型 展示睡眠中断的功能后果 例如抑郁症、与年龄有关的记忆功能障碍和注意力缺陷 多动症。