Fig. 3: Objective and subjective social isolation show different brain signatures implicating the higher-order association cortex versus limbic/saliency brain circuits.

In ~40,000 UK Biobank participants, we quantified the degree to which population variation in grey matter volume can be better explained by loneliness (left half) or social support (right half)³⁷. The outer histograms show the contribution of each of seven examined canonical networks (brain volume measures; the black horizontal line shows the 5–95% highest posterior density [HPD]) to disambiguate lonely individuals (left) and those with social support (right). The x axis denotes the magnitude of each variance parameter value, while the y axis denotes the relative plausibility of these possible parameter values (that is, a higher histogram bar means higher certainty), given the model posterior parameter distributions inferred from the brain data. As shown in the inner brain slices, we examined the structural covariation between the 38 subregions of the hippocampus and 91 subregions of the default network^105,133, by achieving a co-decomposition using a canonical correlation analysis¹⁰⁸. We conducted a rigorous test of how the ensuing subregion patterns diverged in people who reported feeling lonely (left) or having social support (right). Red and blue show positive and negative volume associations, respectively. In recent across-phenome analyses, loneliness was especially associated with depression, anxiety and drug use outcomes³⁷, while social support was mostly linked to overall happiness and satisfaction with family, friends and health¹¹¹. PCC, posterior cingulate cortex; RSC, retrosplenial cortex; dmPFC, dorsomedial prefrontal cortex; STS, superior temporal sulcus; ML, molecular layer; PrS, presubiculum; Sub, subiculum; DG, dentate gyrus; MTG, middle temporal gyrus; vlPFC, ventrolateral prefrontal cortex; HATA, hippocampal–amygdala transition area. Figure reproduced with permission from refs. ^{37,105,111,133}.