Loneliness affects up to 40% of middle-aged and older adults, and is closely associated with major depressive disorder (MDD). However, the relationship between loneliness and neural network functioning during executive cognitive processes, such as working memory, in MDD is still unclear. To address this gap, our study recruited 21 medicated MDD patients (mean age = 52.0 ± 5 years) and 24 matched healthy controls (HC) (mean age = 48.7 ± 6 years) who completed an n-back fMRI task. For behavioural performance, we observed no significant moderating effect of MDD or loneliness on the task condition effect. However, loneliness was positively associated, and MDD was negatively associated, with the functional connectivity between the inferior parietal cortex and the rostral dorsomedial prefrontal cortex (DMPFC) during task performance. Furthermore, an interactive effect of loneliness and MDD was observed on the functional connectivity between the supplementary motor area and the caudal DMPFC during the n-back task, with loneliness showing a positive relationship in the HC group but a negative relationship in the MDD group with the connectivity. Our results indicated that loneliness may be associated with altered neural regulatory functioning on self-referential processing and action control, which may further depend on the individual’s depressive state. These findings can form the theoretical basis for devising intervention programme aimed at improving the mental wellness of the healthy and depressed lonely individuals.

孤独感影响多达 40% 的中老年人，并且与重度抑郁症 (MDD) 密切相关。然而，MDD 中的执行认知过程（如工作记忆）中的孤独感与神经网络功能之间的关系仍不清楚。为了弥补这一差距，我们的研究招募了 21 名完成 n-back fMRI 任务的 MDD 患者（平均年龄 = 52.0 ± 5 岁）和 24 名匹配的健康对照（HC）（平均年龄 = 48.7 ± 6 岁）。对于行为表现，我们没有观察到 MDD 或孤独感对任务条件效应的显着调节作用。然而，在任务执行期间，孤独与下顶叶皮层和头侧背内侧前额叶皮层 (DMPFC) 之间的功能连通性呈正相关，而 MDD 呈负相关。此外，在 n-back 任务期间，观察到孤独感和 MDD 对辅助运动区和尾部 DMPFC 之间的功能连接的交互作用，孤独感在 HC 组中呈正相关，而在 MDD 组中与连接性呈负相关. 我们的研究结果表明，孤独可能与自我参照处理和行动控制的神经调节功能改变有关，这可能进一步取决于个人的抑郁状态。这些发现可以为设计旨在改善健康和抑郁孤独个体的心理健康的干预计划提供理论基础。与孤独感在HC组中呈正相关，而在MDD组中与连通性呈负相关。我们的研究结果表明，孤独可能与自我参照处理和行动控制的神经调节功能改变有关，这可能进一步取决于个人的抑郁状态。这些发现可以为设计旨在改善健康和抑郁孤独个体的心理健康的干预计划提供理论基础。与孤独感在HC组中呈正相关，而在MDD组中与连通性呈负相关。我们的研究结果表明，孤独可能与自我参照处理和行动控制的神经调节功能改变有关，这可能进一步取决于个人的抑郁状态。这些发现可以为设计旨在改善健康和抑郁孤独个体的心理健康的干预计划提供理论基础。