阻塞性睡眠呼吸暂停低通气综合征患者认知功能损害的多模态MRI脑网络研究

Obstructive sleep apnea-hypopnea syndrom (OSAHS) is a common type of sleep-related breathing disorder, caused by repeated obstruction of the upper airway during sleep, leading to a wide range of neurocognitive impairments in learning, memory, attention and, in severe cases, even Alzheimer's disease. Our previous studies have found abnormal local spontaneous brain activity in multiple cognitive-related brain areas in patients with OSAHS, and combined with previous research, we speculated that cognitive impairment may be associated with abnormal patterns of neural functional connectivity at the network-level. However, at present, the patterns of brain network connectivity in OSAHS patients remain unclear. Based on these studies, this project intends to (1) establish large-scale functional and structural brain networks by graph-based complex network analyses, in order to explore imaging biomarkers for multi-modal brain network connectivity in OSAHS patients; (2) establish resting-state networks（RSNs）and investigate the imaging features of altered functional sub-network properties in OSAHS patients; (3) explore the effects of structural and functional network coupling on impaired cognition in OSAHS patients. At the large-scale network level, we employ multimodal MRI to explore abnormal neural network connectivity patterns of cognitive impairment in OSAHS patients, trying to provide image representation for pathophysiological mechanisms and early identification of brain damage in OSAHS patients.

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是睡眠中反复上气道阻塞致呼吸暂停的常见睡眠障碍，会引起学习、记忆及注意等广泛的神经认知功能损害，甚至引发老年痴呆。我们前期研究发现OSAHS患者多个认知相关脑区局部自发神经活动异常，结合以往研究推测认知损害可能与网络水平神经功能连接模式异常有关，但目前对OSAHS脑网络连接模式认识尚不清。基于此，本项目拟应用多模态MRI技术开展：(1)基于连接组学方法构建结构和功能大尺度脑网络，探寻OSAHS患者多模态脑网络连接生物影像学标记。(2)构建OSAHS患者静息态脑网络，探讨子网络功能拓扑属性改变的影像学特征。(3)探讨OSAHS患者脑结构网络和功能网络耦合关系对认知损害的影响。通过对OSAHS患者大尺度网络层面的多模态磁共振脑功能成像研究，探索认知损害的神经网络异常连接模式，试图从网络水平为OSAHS患者脑损害的病理生理机制及早期识别提供影像学表征。

认知功能障碍是阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者常见的临床表现，给家庭和社会带来沉重的负担，客观评估OSAHS患者认知功能损害脑网络机制对临床指导具有重要作用。本项目采集60例OSAHS患者静息态fMRI数据（3D脑容积成像、DTI、BOLD），经过预处理及多种后处理技术，采用fMRI相关技术（度中心度、功能连接、小世界属性等）对OSAHS患者静息态脑网络（RSNs）拓扑属性及脑功能网络连接研究。与正常对照组比较，OSAHS患者存在广泛异常的脑网络，主要表现在左侧枕中回、后扣带皮层、左侧额上回和双侧顶叶小叶的度中心度值显著减低；而右侧眶额叶皮质、双侧小脑后叶和双侧豆状核，延伸到壳核、海马体及颞下回的度中心度值显著增高；内侧前额叶皮层与双侧顶下小叶及左侧顶下小叶与右侧顶下小叶之间的静息态功能连接显著增加；左侧背侧杏仁核与小脑前叶之间的功能连接显著升高，右侧背侧杏仁核与右侧前额叶之间的功能连接显著减低；左侧腹外侧杏仁核与左侧额下回和左侧颞上回之间的功能连接显著升高；右侧腹外侧杏仁核与左侧额下回之间的功能连接显著升高；OSAHS存在小世界属性，但较正常组γ明显下降，但λ和σ显著升高；主要涉及默认网络、额顶控制网络、注意网络及情感网络，部分异常脑网络与认知障碍存在显著关系，这为理解OSAHS患者脑功能网络改变对认知功能的可能机制提供理论基础和技术支持，具有重要的理论意义和潜在的社会效应与经济效应。