Discovery, Replicability, and Generalizability of a Left Anterior Hippocampus' Morphological Network Linked to Self‐Regulation

The human hippocampus is a key region in cognitive and emotional processing, but also a vulnerable and plastic region. Accordingly, there is a great interest in understanding how variability in the hippocampus' structure relates to variability in behavior in healthy and clinical populations. In this study, we aimed to link interindividual variability in subregional hippocampal networks (i.e., the brain grey matter networks of hippocampal subregions) to variability in behavioral phenotype. To do so, we used a multiblock multivariate approach mapping the association between grey matter volume in hippocampal subregions, grey matter volume in the whole brain regions, and behavioral variables in healthy adults. To ensure the robustness and generalizability of the findings, we implemented a cross-cohort discovery and validation framework. This framework utilized two independent cohorts: the Human Connectome Project Young Adult (HCP-YA) cohort and the Human Connectome Project Aging (HCP-A) cohort, enabling us to assess the replicability and generalizability of hippocampal-brain-behavior phenotypes across different age groups in the population. Our results highlighted a left anterior hippocampal morphological network including the left amygdala and the posterior midline structures whose expression relates to higher self-regulation, life satisfaction, and better performance at standard neuropsychological tests. The cross-cohort generalizability of the hippocampus-brain-behavior mapping demonstrates its relevance beyond a specific population sample. Our previous work in developmental populations showed that the hippocampus' head co-maturates with most of the brain during childhood. The current data-driven study further suggests that grey matter volume in the left hippocampal head network would be particularly relevant for self-regulation abilities in adults that influence a range of life outcomes. Future studies should thus investigate the factors influencing the development of this morphological network across childhood, as well as its relationship to neurocognitive phenotypes in various brain diseases.