基于蓝斑功能连接探讨失眠发生的中枢机制:一项静息态功能磁共振成像研究

Exploring the central mechanism of insomnia through the functional connectivity of locus coeruleus:A resting-state functional magnetic resonance imaging study

目的 利用脑功能磁共振成像(functional magnetic resonance imaging, fMRI)技术研究失眠患者静息态下蓝斑的功能连接(functional connectivity, FC)变化。材料与方法 前瞻性纳入59例失眠患者及30例健康对照者,对受试者进行匹兹堡睡眠量表(Pittsburgh Sleep Quality Index, PSQI)、汉密尔顿抑郁量表(Hamilton Depression Scale, HAMD)、汉密尔顿焦虑量表(Hamilton Anxiety Scale, HAMA)、过度觉醒量表(Hyperarousal Scale, HAS)评分,并采集静息态脑fMRI数据,以蓝斑为感兴趣区,计算与全脑所有体素的FC值,使用t检验比较两组间差异,提取有差异脑区的脑FC值,与临床量表评分进行相关性分析。结果 失眠患者与健康对照组在年龄、性别及受教育年限上差异无统计学意义。与健康对照组相比,失眠患者蓝斑与右侧额中回的FC值升高(GRF校正,体素水平P<0.001,团块水平P<0.05),并与PSQI(r=0.40,P<0.001)、HAMD(r=0.39,P<0.001)、HAMA(r=0.39,P<0.001)、HAS(r=0.46,P<0.001)评分均呈正相关。结论 失眠患者蓝斑与右侧额中回的FC增强可能与失眠患者过度觉醒状态有关,并且可能导致失眠患者的焦虑抑郁情绪,从而引发睡眠质量下降。该研究为失眠的过度觉醒假说提供了影像学依据,证明了蓝斑在睡眠觉醒过程的重要作用,进一步揭示了失眠的发病脑功能机制,为失眠治疗靶点的选择提供了新思路。

Objective: To explore the functional connectivity(FC) changes of the locus coeruleus(LC) in the resting state of insomnia patients utilizing functional magnetic resonance imaging(fMRI). Materials and Methods: Fifty-nine patients with insomnia disorder(ID) and 30 healthy controls were included. Pittsburgh Sleep Quality Index(PSQI), Hamilton Depression Scale(HAMD), Hamilton Anxiety Scale(HAMA), and Hyperarousal Scale(HAS) scores were assessed, and resting-state fMRI data were collected. The FC values with all voxels in the brain were calculated using the LC as the region of interest, and the differences between the two groups were compared using a t-test. The FC values of the brain regions with differences were extracted and correlated with the clinical scale scores.Results: There were no statistical differences in age, gender, or education between insomnia patients and healthy controls. In comparison to the healthy group, ID patients had increased FC between the LC and the right middle frontal gyrus(GRF correction, P-cluster<0.001,P-cluster<0.05), which was positively correlated with PSQI(r=0.40), HAMD(r=0.39), HAMA(r=0.39), and HAS(r=0.46) scores(all P<0.001). Conclusions: Enhanced FC of the LC with the right middle frontal gyrus may be associated with hyperarousal states and may contribute to anxiety and depression in insomnia patients, resulting in decreased sleep quality. This study provided an imaging basis for the hyperarousal theory, demonstrated the important role of LC in the sleep-wake process, further revealed the brain functional mechanism of insomnia, and offered new ideas for the selection treatment targets of insomnia.