睡眠依赖性前扣带皮层兴奋-抑制平衡改变将BOLD-CSF耦合变化与阻塞性睡眠呼吸暂停的认知表现联系起来

文献信息

中文摘要

目的： 皮层类淋巴功能障碍和兴奋-抑制失衡在阻塞性睡眠呼吸暂停（OSA）相关认知障碍中的作用需要进一步研究。本研究旨在探讨OSA中睡眠相关的类淋巴功能和神经递质变化及其与认知的关系。
方法： 87名参与者（50名OSA，37名对照）完成了睡前MRI，随后进行整夜PSG记录，以及睡后MRI以评估睡眠依赖的类淋巴和神经递质变化。在全局皮层、前扣带皮层（ACC）、后扣带皮层（PCC）和默认模式网络（DMN）皮层中评估了静息态血氧水平依赖（BOLD）信号和脑脊液（CSF）信号（BOLD-CSF耦合），这是一种间接的类淋巴相关成像代理。在ACC和PCC中测量了MRS衍生的γ-氨基丁酸（GABA）和谷氨酸/谷氨酰胺（Glx）水平，作为兴奋-抑制（E/I）平衡的间接神经化学指标。采用一般线性模型、线性混合效应模型、相关分析和调节分析来检查组间差异、BOLD-CSF耦合和神经递质的过夜变化及其与认知表现的关系。
结果： 在中重度OSA组中，睡前全局和ACC-BOLD-CSF耦合弱于对照组，ACC-GABA显示出组×时间交互作用（ηp² = 0.105，p-FDR = 0.049），仅在对照组中观察到显著的过夜下降（Cohen's d = 0.75，p-FDR = 0.007）。ACC-BOLD-CSF耦合和ACC-E/I的过夜变化幅度越大，独立地与更差的认知相关。ACC-E/I变化也调节了耦合-认知关系（β = 0.590，p = 0.015），仅在E/I变化幅度较小时存在显著的负相关（β = -0.729，p = 0.002）。
结论： 我们的发现表明，OSA严重程度与ACC特异性BOLD-CSF解耦和ACC-GABA过夜下降的破坏有关。过夜E/I变化的幅度调节了BOLD-CSF耦合变化与认知表现之间的关联。这些初步发现强调了ACC-BOLD-CSF耦合和神经化学改变与OSA相关认知障碍的潜在相关性。需要更大样本量的未来研究来证实这些发现。

英文摘要

OBJECTIVE: The roles of cortical glymphatic dysfunction and excitation-inhibition imbalance in cognitive impairment associated with obstructive sleep apnea (OSA) require further study. This study aimed to investigate sleep-related glymphatic function and neurotransmitter changes in OSA and their relationships with cognition.
METHODS: Eighty seven participants (50 OSA, 37 controls) completed a pre-sleep MRI, followed by an overnight PSG recording, and a post-sleep MRI to assess sleep-dependent glymphatic and neurotransmitter changes. Resting-state blood-oxygen-level-dependent (BOLD) signals and cerebrospinal fluid (CSF) signals (BOLD-CSF coupling), an indirect glymphatic-related imaging proxy, were assessed in the global cortex, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and default mode network (DMN) cortex. MRS-derived gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels were measured in the ACC and PCC as indirect neurochemical measures of excitation-inhibition (E/I) balance. General linear models, linear mixed-effects models, correlation analyses, and moderation analyses were employed to examine group differences, overnight changes in BOLD-CSF coupling and neurotransmitters, and their relationships with cognitive performance.
RESULTS: In the moderate-to-severe OSA group, pre-sleep global and ACC-BOLD-CSF coupling were weaker than in controls, and ACC-GABA showed a group × time interaction (ηp 2 = 0.105, p-FDR = 0.049), with a significant overnight decrease observed only in controls (Cohen's d = 0.75, p-FDR = 0.007). Greater magnitudes of overnight change in both ACC-BOLD-CSF coupling and ACC-E/I were independently associated with worse cognition. ACC-E/I change also moderated the coupling-cognition relationship (β = 0.590, p = 0.015), with a significant negative association only at smaller magnitudes of E/I change (β = -0.729, p = 0.002).
CONCLUSION: Our findings suggest that OSA severity is associated with ACC-specific BOLD-CSF decoupling and a disrupted overnight decline in ACC-GABA. The magnitude of overnight E/I variation moderated the association between BOLD-CSF coupling variation and cognitive performance. These preliminary findings highlight the potential relevance of ACC-BOLD-CSF coupling and neurochemical alterations to OSA-related cognitive impairment. Future studies with larger sample sizes are needed to confirm these findings.