生命意义感 (meaning in life, MIL) 作为心理健康的重要保护因子，近些年来引起了心理学和健康领域研究的关注。其被认为是一种对于生命意义的心理感受，涉及人们对自身及其生活的连贯理解、目的，和重要性的感知，在缓冲孤独感方面起着重要作用。而孤独感是抑郁症和其他心理疾病的一个重要危险因子。相当多的证据表明，生命意义感的产生涉及了广泛分布的大脑活动，但这种活动如何在功能上进行整合，然后缓冲孤独感仍未得到充分研究。而无论是生命意义感还是孤独感，都对心理健康产生了重要影响，而大脑功能整合如何经由生命意义感和孤独感对心理健康产生影响也值得进一步探讨。在研究一中，为了获得与生命意义感相关的大脑功能整合，我们基于人类连接组项目 (Human Connectome Project，HCP) 的970个成年人被试的静息态功能核磁共振成像数据，使用全脑连接强度 (global brain connectivity, GBC) 和功能连接 (functional connectivity) 作为全脑功能整合的代表，对脑区的功能整合与个体生命意义感之间的关系进行了研究。我们发现，右前脑岛 (right anterior insula, rAI) 的全脑连接强度和其与DLPFC和PCC的功能连接可以显著预测个体生命意义感。在研究二中，我们进行了简单中介分析，研究大脑如何在生命意义感的中介下影响孤独感，结果发现生命意义感完全中介了该功能整合节点的全脑连接强度和其与背后侧前额叶 (dorsal lateral prefrontal cortex, DLPFC) 和后扣带回 (posterior cingulate cortex, PCC) 的功能连接对孤独感的影响。而神经质能够通过调节生命意义感到孤独感的路径，调节大脑功能整合对孤独感的影响。在研究三中，我们对心理疾病的相关指标进行降维，获得了心理疾病的共有维度和不同分类维度 (内化症状和外化症状)。而后，我们以生命意义感和孤独感为链式中介变量，以能暗示心理疾病倾向的指标为因变量，检验了链式中介模型，发现间接效应显著。而该链式中介对内化症状的影响高于对外化症状的影响，且神经质对内化症状的调节显著，而对外化症状的调节不显著。这些发现表明，rAI是生命意义感和孤独感的一个关键枢纽，并能够经由这条路径进一步影响心理健康。它的功能整合可以作为预测个体生命意义感、孤独感和心理健康的生物标志物。

Meaning in life (MIL), as a protective factor for mental health, recently has caught attention to researchers in the field of psychology and health. Defined as a feeling of meaningfulness, it refers to people’s sense of coherence, purpose, and mattering, and is a representation of positive adjustive mechanism to buffer loneliness - an important indicator of depression and other psychological disorders. Various evidence proves that MIL arises from widely distributed brain activity, but how such activity is functionally integrated and then influences loneliness is still understudied. Moreover, if this influence on loneliness could sequentially affect mental health is also worthwhile to explore. In study 1, We here examined how the functional integration of brain regions is related to individual MIL based on resting-state functional magnetic resonance imaging data from Human Connectome Project (N=970). We found that the global brain connectivity (GBC) of the right anterior insula (rAI) and rAI’s functional connectivity with dorsal lateral prefrontal cortex (DLPFC) and posterior cingulate cortex (PCC) could significantly predict individual MIL. In study 2, mediation analyses were conducted to investigate how the brain influences loneliness with MIL’s mediation, and it was revealed that MIL fully mediates the effect of this hub on loneliness. Neuroticism could moderating the mediating model through the path from MIL to loneliness. In study 3, we test the serial mediation model with MIL and loneliness as serial mediation variables, and indexes indicating meantal health as dependent variable. At first, we got the general factor and different categories (internalizing/externalizing) by utilizing the confirmatory factor analysis. Next, we executed serial mediation analyses and discovered the indirect effects of this mediation model are significant, and the indirect effect of the mediation model with internalizing as dependent variable is higher than that with externalizing. Neuroticism’s moderating effect shows significance in the serial mediating model with internalizing as dependent variable rather than that with externalizing. These findings suggest that the rAI is a key hub for MIL and loneliness, and subsequently influence mental health. Its functional integration could be used as a biomarker to predict individual MIL, loneliness, and mental health.