The relationship between loneliness and working-memory-related frontoparietal network connectivity in people with major depressive disorder

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.