共病失眠与睡眠呼吸暂停中丘脑纹状体功能网络的独特失调

文献信息

中文摘要

研究目的： 共病失眠与睡眠呼吸暂停（COMISA）是一种常见且临床具有挑战性的表型，但将其与孤立性阻塞性睡眠呼吸暂停（OSA）区分开来的神经基础仍不清楚。我们采用多模态图论方法，以识别与COMISA表型相关的结构和功能网络模式。
方法： 我们分析了124名男性参与者（45名对照、58名OSA和21名COMISA）。结构协方差网络由区域灰质体积数据得出，功能网络由静息态fMRI得出。对加权、无向网络量化图指标——包括强度、聚类系数（CC）、效率和接近中心性（CloC）——以评估全局和节点拓扑属性。
结果： 功能网络分析显示，与对照组相比，两个患者组均存在显著的全局超连接。关键的是，与OSA相比，COMISA表现出独特的功能模式，其特征是丘脑纹状体回路内节点指标（CC和CloC）显著升高，具体涉及双侧丘脑和壳核。在整个队列中的探索性分析提示，这些节点指标与失眠和抑郁症状的严重程度可能存在正相关。相比之下，结构协方差网络未显示显著的组间差异，表明两种模态之间存在分离。
结论： 我们的发现提示，COMISA呈现出一种独特的功能模式，这与回路层面的失调一致，特别是在丘脑纹状体轴内。这种位于觉醒调节回路内的皮层下模式，为COMISA中经常观察到的临床复杂性和治疗抵抗提供了潜在的病理生理学解释。

英文摘要

STUDY OBJECTIVES: Comorbid insomnia and sleep apnea (COMISA) is a prevalent and clinically challenging phenotype, yet the neural substrates distinguishing it from isolated obstructive sleep apnea (OSA) remain elusive. We employed a multimodal graph theoretical approach to identify the structural and functional network patterns associated with the COMISA phenotype.
METHODS: We analyzed 124 male participants (45 controls, 58 OSA, and 21 COMISA). Structural covariance networks were derived from regional gray matter volume data, and functional networks from resting-state fMRI. Graph metrics-including strength, clustering coefficient (CC), efficiency, and closeness centrality (CloC)-were quantified for weighted, undirected networks to assess global and nodal topological properties.
RESULTS: Functional network analysis revealed significant global hyper-connectivity in both patient groups compared to controls. Crucially, COMISA demonstrated a distinct functional pattern compared to OSA, characterized by significantly elevated nodal metrics (CC and CloC) within thalamostriatal circuits, specifically involving the bilateral thalamus and putamen. Exploratory analyses across the cohort suggested possible positive associations between these nodal metrics and the severity of insomnia and depressive symptoms. In contrast, structural covariance networks showed no significant group differences, indicating a dissociation between the two modalities.
CONCLUSIONS: Our findings suggest that COMISA presents a distinct functional pattern, which is consistent with circuit-level dysregulation, specifically within the thalamostriatal axis. This subcortical pattern within arousal-modulating circuits offers a potential pathophysiological explanation for the clinical complexity and treatment resistance frequently observed in COMISA.