Neural Sites Mediating Obstructive Sleep Apnea

该项目将调查与阻塞性睡眠呼吸暂停（OSA）相关的睡眠呼吸障碍的结构和功能神经解剖学，这是一种影响高达4%人口的综合征。我们过去的研究表明，OSA和心力衰竭患者在调节呼吸模式、呼吸暂停后的开始、上呼吸道肌肉组织的精细控制和血压的小脑、边缘和皮质区域表现出显著的灰质损失。通过功能性磁共振成像（tMRI），我们还发现，在灰质损失重叠的大脑区域，对呼吸和心血管挑战产生了异常的神经反应。OSA中一些表现出结构和功能异常的区域接收轴突投射，对低氧血症和兴奋性毒性异常敏感，这表明某些异常可能是由反复缺氧发作引起的。其他脑灰质丢失或功能障碍的部位是单侧的，或者是在对低氧血症不太敏感的灌注良好的区域，这表明有可能

The project will investigate the structural and functional neuroanatomy of sleep disordered breathing associated with obstructive sleep apnea (OSA), a syndrome that affects up to 4 % of the population. Our studies in the past period demonstrated that OSA and heart failure patients show significant gray matter loss in cerebellar, limbic, and cortical areas that mediate patterning of breathing, initiation of respiration following a pause, fine control of upper airway musculature, and blood pressure. With functional magnetic resonance imaging (tMRI), we also found abnormal neural responses develop to breathing and cardiovascular challenges in brain regions that overlap areas of gray matter loss. Some of the regions that showed structural and functional abnormalities in OSA receive axonal projections that are extraordinarily sensitive to hypoxemia and excitotoxicity, suggesting that certain abnormalities may resuk from repeated hypoxic episodes. Other brain sites with gray matter loss or dysfunction were unilateral or were in well-perfused areas that are less sensitive to hypoxemia, suggesting the possibility of maldevelopment or neural damage pre-existing the syndrome. We will use high resolution volumetric structural MRI and diffusion tensor MRI in OSA patients and controls to a) demonstrate axonal damage in olivo-Purkinje climbing fibers of the cerebellum and perforant path fibers to the CA1 region of the hippocampus, and b) define specific areas of gray matter loss in hippocampal, cerebellar cortex and deep nuclei, and insular, frontal and parietal cortex. Functional MRI will be used to evaluate neural responses in affected areas to a cold pressor challenge at higher spatial and temporal resolution. The studies have the potential to reveal the causative neural deficits that lead to the upper airway atonia, out-of-synchrony respiratory action, and high sympathetic tone associated with disordered breathing during sleep. The determination of axonal and gray matter loss resulting from repeated hypoxia during sleep represents a significant and necessary forward step in the development of therapeutic interventions.