基底前脑自发神经活动对原发性失眠患者皮质-边缘系统的神经调节机制研究

The primary insomnia (PI) is a common sleep disorder, however, the exact of neural mechanisms are still unclear. The previous studies of our group and other groups have shown that the abnormal function and structure of cortico-limbic system associated with hyper-arousal in PI patients.The latest studies have shown that the basal forebrain (BF), as one of hub regions regulating sleep activity, participates in the regulation of extensive neural network and has high synergistic activity with the brain regions of the cortical-limb system. The results of our pilot study indicate that BF has functional and structural changes in PI. Therefore, we speculate the BF may play an important role in regulating the cortical-marginal system in patients with PI, leading to abnormal cortical-marginal system in PI patients. This project will collect multimodal magnetic resonance imaging datasets, refer to sleep-related behavioral measures, combined with a variety of imaging data analysis methods and dynamic causal model, to explore the abnormal spontaneous neural activity of BF, its functional connectivity with cortical-limbic system as well as the brain network properties in patients with PI; to further study the hierarchical relationship between BF and cortical limbic system in patients with PI, and to clarify neuromodulation effect of BF on cortico-limbic system. This project provides evidence for understanding the deep brain neural mechanism of PI patients in theory. In addition, BF can be used as a potential target area for the treatment of insomnia, which provides a new idea for human understanding of sleep mechanism and treatment of insomnia.

原发性失眠（PI）是常见的睡眠障碍，但其确切的神经机制尚不清楚。我们的前期研究表明与“过度觉醒”相关的皮质-边缘系统脑区存在功能及结构的异常。最新的研究表明基底前脑（BF）作为调节睡眠的中枢，参与广泛的大脑神经网络调节，与皮质-边缘系统相关脑区具有较高的协同活动。我们的初步研究结果发现BF在PI中存在功能及结构改变。据此我们推测BF可能参与PI患者中皮质-边缘系统脑区的调控，引发PI患者皮质-边缘系统异常。本项目将采用多模态磁共振成像技术结合多种影像数据分析及动态因果模型，联合睡眠相关的指标，探索PI患者BF自发神经活动及其与皮质-边缘系统功能连接及网络属性的异常，探索PI患者BF与皮质-边缘系统间的层级结构关系，明确BF对皮质-边缘系统的神经活动调节及其与睡眠相关指标的关系。本项目将为理解PI患者深层次大脑神经机制提供证据，也可将BF作为治疗失眠的潜在靶区域，为治疗失眠提供新的治疗思路。

原发性失眠是常见的睡眠障碍，但其确切的神经机制尚不清楚。我们的前期研究表明与“过度觉醒”相关的皮质-边缘系统脑区存在功能及结构的异常。最新的研究表明基底前脑（BF）作为调节睡眠的中枢，参与广泛的大脑神经网络调节，与皮质-边缘系统相关脑区具有较高的协同活动。但是BF是否存在结构、自发神经活动及功能连接异常？BF是否调控皮质-边缘系统，进而引发PI患者中皮质-边缘系统异常？基于这些问题，本项目基于大样本的失眠患者及正常对照组，采用了多模态磁共振成像技术结合多种影像数据分析，联合睡眠相关的指标，取得以下发现: 1) 失眠患者中基底前脑(BF)的不同亚区的功能连接存在显著的差异；具体表现为相对于正常对照组，失眠患者中Ch4与觉醒相关的重要脑区中脑的功能连接显著增高；而Ch_123与内侧额上回的功能连接显著下降。BF亚区的功能连接的改变可能反映了失眠患者中异常和特定的BF亚区神经递质投射; 2)相对于正常对照组，失眠患者中BF不存在自发神经活动和脑区体积的异常；后期我们将进一步对失眠进行亚组分析以期获得更多的发现; 3)失眠患者中额上回异常的网络中心度和肠道微生物以及睡眠效率相关; 4) 随着失眠的严重阶段的进展，与睡眠、情绪和认知功能相关的大脑区域的灰质体积逐渐增加，主要包括前扣带以及颞中回，这表明肥大的皮质-边缘系统脑区的皮质形态学可能是失眠神经生物学的基础；基于我们的发现，本项目为理解原发性失眠患者的深层次大脑神经机制提供证据，在应用上可将BF乙酰胆碱神经元作为治疗失眠的潜在靶区域，治疗失眠提供新的思路。