Urban maps of the brain: associations between city living, brain anatomy, and mental and cognitive health

Urbanization has profoundly transformed the living conditions of a large proportion of the global population and continues to expand worldwide. Urban environments relate to human health through multiple pathways, including lifestyle factors, social conditions, and environmental exposures. These associations reflect not only urban living itself but also the geographic context and spatial organization of cities. Urbanicity may therefore influence physical health, mental health and cognitive functioning. In this context, the brain represents a potential biological pathway linking urban environments to behavioral outcomes. Despite increasing research on environmental exposures, brain structure, mental health, and cognition, integrative approaches that combine these domains while accounting for geographic context remain limited. This thesis aims to address these gaps by developing an analytical framework that integrates georeferenced environmental exposures and neurobehavioral data at the individual level. It combines geospatial epidemiology, neuroscience, and outcome-wide analysis within urban exposome frameworks to examine how environmental conditions in cities relate to brain structure and behavioral health. The thesis is structured around three case studies. The first two use data from the CoLaus|PsyCoLaus and BrainLaus cohorts in Lausanne, Switzerland. In these, we applied spatially explicit approaches to investigate neurobehavioral outcomes in an urban setting. The analyses identified geographic patterns of brain structure, mental health and cognitive performance across the city and characterized the environmental exposures associated with these patterns. Spatial modeling further revealed localized associations operating at different spatial scales, highlighting the importance of considering the geographic context when studying environmental determinants of neurobehavioral health. In the third study, we extended the analysis to maternal mental health during pregnancy using data from the Barcelona Life Study Cohort (BiSC) in Spain. We applied an outcome-wide exposome framework to enable the simultaneous assessment of multiple urban environmental exposures and multiple mental health outcomes. The findings indicated that certain environmental exposures showed consistent associations with general psychological distress, illustrating the potential of many-to-many analytical approaches to identify environmental factors related to multiple dimensions of mental health. Overall, this thesis demonstrates the value of combining spatially explicit analytical methods with exposome approaches to study brain, mental, and cognitive health in urban environments across different populations. By identifying geographic patterns of these outcomes and modifiable environmental exposures associated with them, this work contributes to bridging environmental health research and urban policy, and highlights potential targets for public health and urban planning interventi