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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., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Motor performance (MP) is essential for functional independence and well-being, particularly in later life. However, the relationship between behavioural aspects such as sleep quality and depressive symptoms, which contribute to MP, and the underlying structural brain substrates of their interplay remains unclear. This study used three population-based cohorts of younger and older adults (n=1,950) from the Human Connectome Project-Young Adult (HCP-YA), HCP-Aging (HCP-A), and enhanced Nathan Kline Institute-Rockland sample (eNKI-RS). Several canonical correlation analyses were computed within a machine learning framework to assess the associations between each of the three domains (sleep quality, depressive symptoms, grey matter volume (GMV)) and MP. The HCP-YA analyses showed progressively stronger associations between MP and each domain: depressive symptoms (unexpectedly positive, r=0.13, SD=0.06), sleep quality (r=0.17, SD=0.05), and GMV (r=0.19, SD=0.06). Combining sleep and depressive symptoms significantly improved the canonical correlations (r=0.25, SD=0.05), while the addition of GMV exhibited no further increase (r=0.23, SD=0.06). In young adults, better sleep quality, mild depressive symptoms, and GMV of several brain regions were associated with better MP. This was conceptually replicated in young adults from the eNKI-RS cohort. In HCP-Aging, better sleep quality, fewer depressive symptoms, and increased GMV were associated with MP. Robust multivariate associations were observed between sleep quality, depressive symptoms and GMV with MP, as well as age-related variations in these factors. Future studies should further explore these associations and consider interventions targeting sleep and mental health to test the potential effects on MP across the lifespan., Competing Interests: Conflict of Interest Disclosures The authors declare no conflicts of interest.

Identifying associations between interindividual variability in brain structure and behaviour requires large cohorts, multivariate methods, out-of-sample validation and, ideally, out-of-cohort replication. Moreover, the influence of nature vs nurture on brain-behaviour associations should be analysed. We analysed associations between brain structure (grey matter volume, cortical thickness, and surface area) and behaviour (spanning cognition, emotion, and alertness) using regularized canonical correlation analysis and a machine learning framework that tests the generalisability and stability of such associations. The replicability of brain-behaviour associations was assessed in two large, independent cohorts. The load of genetic factors on these associations was analysed with heritability and genetic correlation. We found one heritable and replicable latent dimension linking cognitive-control/executive-functions and positive affect to brain structural variability in areas typically associated with higher cognitive functions, and with areas typically associated with sensorimotor functions. These results revealed a major axis of interindividual behavioural variability linking to a whole-brain structural pattern., (© 2022. The Author(s).)

The study of associations between inter-individual differences in brain structure and behaviour has a long history in psychology and neuroscience. Many associations between psychometric data, particularly intelligence and personality measures and local variations of brain structure have been reported. While the impact of such reported associations often goes beyond scientific communities, resonating in the public mind, their replicability is rarely evidenced. Previously, we have shown that associations between psychometric measures and estimates of grey matter volume (GMV) result in rarely replicated findings across large samples of healthy adults. However, the question remains if these observations are at least partly linked to the multidetermined nature of the variations in GMV, particularly within samples with wide age-range. Therefore, here we extended those evaluations and empirically investigated the replicability of associations of a broad range of psychometric variables and cortical thickness in a large cohort of healthy young adults. In line with our observations with GMV, our current analyses revealed low likelihood of significant associations and their rare replication across independent samples. We here discuss the implications of these findings within the context of accumulating evidence of the general poor replicability of structural-brain-behaviour associations, and more broadly of the replication crisis., (© 2022. The Author(s).)