Loneliness is linked to specific subregional alterations in hippocampus-default network co-variation

Social interaction complexity makes humans unique. But in times of social deprivation this strength risks to expose important vulnerabilities. Human social neuroscience studies have placed a premium on the default network (DN). In contrast, hippocampus (HC) subfields have been intensely studied in rodents and monkeys. To bridge these two literatures, we here quantified how DN subregions systematically co-vary with specific HC subfields in the context of subjective social isolation (i.e., loneliness). By co-decomposition using structural brain scans of ∼40,000 UK Biobank participants, loneliness was specially linked to midline subregions in the uncovered DN patterns. These association cortex signatures coincided with concomitant HC patterns implicating especially CA1 and molecular layer. These patterns also showed a strong affiliation with the fornix white-matter tract and the nucleus accumbens. In addition, separable signatures of structural HC-DN co-variation had distinct associations with the genetic predisposition for loneliness at the population level.