WORKING MEMORY IN OBSTRUCTIVE SLEEP APNEA-AN fMRI STUDY

描述(由申请人提供)： 阻塞性睡眠呼吸暂停(OSA)与更高级别的异常有关 执行认知功能。颈椎的精确神经解剖定位 这些赤字是未知的。高管认知的生理关联 功能障碍的定义很模糊，治疗后的恢复可能是 不完整。该项目提出了一种神经成像技术的新用途， 功能磁共振成像(FMRI)和精确的神经行为 方案，以定位功能障碍的神经解剖学位置。其他内容 协议将分离出这些特定的生理关联 神经认知异常，如睡眠碎片、睡眠剥夺、 以及夜间氧气减饱和，并将它们与区域变化联系在一起 皮质功能。我们将调查未完全恢复的原因 鼻腔正压治疗时的执行功能。 工作记忆是一种大脑系统，它提供临时存储和 操纵执行复杂认知任务所需的信息，以及 它有助于实现几项行政职能。N-back范式是一种 在MU研究中广泛使用的工作记忆探针，通常是 与前额叶背外侧皮质(DLPFC)激活有关的前 扣带回和后顶叶皮质。我们已将这项任务调整为2- 适用于阻塞性睡眠呼吸暂停综合征患者的背部使用难度。我们的初步数据显示 阻塞性睡眠呼吸暂停患者工作记忆容量的可逆性(经治疗)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)阻塞性睡眠呼吸暂停综合征患者DLPFC的激活减少， 在工作记忆测试中相对于后顶叶皮质。2)睡眠 剥夺或碎片化，但不是夜间低氧破坏工作记忆 在正常受试者中。3)。治疗后残留异常由以下原因引起 持续的睡眠碎片，而不是先前的低氧暴露。 私家侦探接受过普通医学、神经学、睡眠障碍和 功能神经成像。拟议的项目将在 睡眠障碍、认知神经科学和 哈佛系统内的功能性核磁共振成像。相关的研究环境是 在参与机构方面特别丰富--基础和应用 睡眠的神经生物学、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核磁共振物理方面的培训， 应用核磁共振，统计和研究方法，伦理学，临床规划 研究和认知神经科学。眼前的职业目标是获得 临床应用功能磁共振成像的必要技能和确定功能 减少工作负荷的定位、病因和恢复的神经回路 2-back任务范式对阻塞性睡眠呼吸暂停患者记忆容量的影响从长远来看 职业目标是开发睡眠功能的模型，通过 演示睡眠中断在某些情况下的功能后果 如抑郁症、与年龄相关的记忆功能障碍和注意力缺陷 多动症。

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.