Differential increase of hippocampal subfield volume after socio-affective mental training relates to reductions in diurnal cortisol

The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3 months mental Training Modules geared towards nurturing (a) attention-based mindfulness, (b) socio-affective, or (c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3 months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.